Download Virus Tumor Antigens: Specific Fingerprints?

[CANCER RESEARCH 26 Part 1, 2018-2024,September 1966]
Virus Tumor Antigens: Specific Fingerprints?
KARL HABEL
Laboratory of Biology of Viruses, Xational Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland
Summary
Immunologically new antigens of at least 2 general types have
been demonstrated in cells transformed, both in vivo and in
vitro, by viruses. In fact, this now appears to be true in all virusinduced tumors. The specificity of these antigens is determined
by the inducing virus and is the same in tumors of a variety of
histologie types and in different species. These antigens are
foreign to the immunologically competent host and are reacted
to by either homograft rejection or antibody formation, or both.
Certain of these antigens are also produced early in the course of
a lytic infection by the tumor viruses and may well represent
virus-coded specific enzymes required for replication of certain
viral constituents, such as their nucleic acids. There are a number
of experimental facts consistent with the interpretation that the
existence of these antigens reflects the continuing presence of
viral genetic material in the transformed cell even when infec
tious virus cannot be demonstrated.
Introduction
Although it has been known for over 50 years that certain
viruses can induce the formation of tumors, it is only in the last
few years that evidence has shown this induction to be the direct
effect of virus infection of the single cell it transforms. This
new knowledge has naturally led to the secondary question of
what happens to the virus after transformation of the cell. In
the case of UNA tumor viruses, it has become apparent that,
in most cases, virus replication and release continue along with
survival and multiplication of the transformed cell. However,
in many cases the cell transformed by a DNA tumor virus is
free of demonstrable infectious virus. This has led to the very
fundamental question whether persistence of the DNA virus or
viral materials occurs at all or is essential to the continuation of
the transformed state or whether the virus has had a sort of
"hit and run" relationship to the cell it transformed.
There is currently being accumulated more and more evidence
that viral material, specifically viral genome, does indeed persist
in these situations. Thus, induction of infectious virus replication
(4), extraction of infectious viral nucleic acid (17), and indirect
demonstration of the presence of viral genome in association with
cell genome (2) have established this as a fact in some systems.
One additional piece of evidence supporting the thesis that viral
genome persists has been the demonstration of specific antigens
in cells transformed by viruses. That these antigens are the
fingerprints of the viral genomes persisting in the tumor cells
seems a logical conclusion at the present state of our knowledge.
It is the purpose of this report to discuss the biologic nature of
these antigens and their relationship to the virus and the cell,
2018
as well as their implications in oneogenesis. Major emphasis will
be placed on the antigens associated with cells transformed by
DNA tumor virus, and detailed results will be presented only for
recent studies with the CF1 antigen in the polyoma-infected or
transformed cell.
Biologic
Properties
of Antigens
How many different new specific antigens may be present in
virus-transformed cells is not known. In the case of the DNA
virus-induced tumors, at the present time there appear to be at
least 2 types of new antigens based on the methods used to
demonstrate them—the Homotransplantation and the serologie
types. The homotransplantation antigen can be demonstrated
only in the intact animal by showing resistance to tumor chal
lenge (7, 30), whereas the serologie antigen can be measured
in vitro through the use of antibodies produced by tumor-bearing
or tumor-immunized animals. Cytotoxicity (3, 22, 31), comple
ment-fixation (16), and immunofluorescence (18, 24) are some
of the technics used to demonstrate the serologie type antigens.
In Table 1 are summarized some of the important biologic
properties of the 2 types of antigens in DNA tumor virus sys
tems. 13oth types are found in tumors of various organs (29),
and in tissue culture cells transformed by the viruses (9, 12).
One of the intriguing aspects of these tumor antigens is the fact
that the serologie type antigen is also made during the course of
lytic infection (5, 26, 27). More detailed experimental results
on this will be presented later. Thus far, there is no evidence
available concerning the presence or absence of the homotrans
plantation type antigen during lytic infection.
Perhaps the most significant property of these new antigens
is their specificity. The specific determinant is the virus that
originally caused the tumor (12, 16) or cell transformation, and
this specificity is not influenced by the histologie type of the
tumor, the strain of animal, or even the species of animal whose
cells are involved. Both types of antigens can be demonstrated
to cross-react in cells transformed by 1 virus in such widely
disparate species as hamster and man (6, 13). However, CF
antigens present in hamster tumors induced by certain types of
adenoviruses cross-react (16), as do the CF antigens produced
in several different RNA virus avian (1) and mouse leukoses
(14) and those involved in some cytotoxic tests of mouse leu
kemia cells (23).
1The abbreviations used are: CF, complement-fixing or comple
ment fixation; FUDR, 5-fluorodeoxyuridine; METC, mouse
embryo tissue culture; HETC, hamster embryo tissue culture;
PFU, plaque-forming units.
CANCER RESEARCH VOL. 26
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.
Virus Tumor Antigens
TABLE 1
PROPERTIESOF 2 TYPES OF ANTIGENSPRODUCED
BY I)\A TUMORVIRUSES
HOMOTRANS
PLANTATION
ANTIGEN
CF°ANTIGEN
infectious virus appearing after about 24-48 hr (35). Cell lysis
is usually not 100%, and a small fraction of the cells may be
morphologically transformed. This transformation is demon
strated by the ability of single cells to form clones showing a
lack of contact inhibition (28). On prolonged cultivation of such
infected mass cultures a "carrier culture" is frequently estab
lished in which virus replication continues along with cell divi
sion and culture growth (9). As has been found with lytic infec
tion of monkey kidney cells with SV-40 virus (27) and of KB
cells with adeno 12 virus (5), we have shown that during the
Surface
Nucleus
lytic infection cycle of polyoma there appears a new antigen
(T-antigen), \vhich reacts with antibodies against the serologie
antigen of polyoma tumors. These lytic antigens have been
demonstrated both by the fluorescent antibody staining technic
and by CF.
It has been typical of these new antigens in the 3 systems that
they appear early in the lytic cycle, even before the appearance
of new infectious virus or viral coat antigens. In fact, they tend
" CF, complement-fixation.
to decrease in amount or disappear in the later stages of the
lytic infection when new virus is reaching its peak level. Chart 1
Evidence concerning the intracellular location of the tumor shows our results in the polyoma-mouse embryo culture system.
In order to obtain some information concerning the relation
antigens is limited. However, the CF antigen in SV-40 and
ship between these early lytic antigens and the various stages
polyoma cells appears to be in the nucleus, as demonstrated
of the virus replicative cycle, the effect of various metabolic
by fluorescent antibody staining (Ref. 24, and data to be pub
inhibitors on the appearance of the antigen has been studied.
lished by K. K. Takemoto, R. A. Malmgren, and K. Habel)
and the homotransplantation antigen in the cell wall (33). In In the SV-40-monkey kidney culture system, Rapp et al. (25)
systems where the cytotoxic test is effective, the antigen is also have postulated a sequence for the time of effect of various
located in the cell wall (31). In fact, in cells transformed by the inhibitors and have shown a lack of inhibition of T-antigen
production with inhibitors of DNA synthesis. Gilead and GinsRNA tumor viruses, which, in general, appear to be myxovirusburg (5) have confirmed the lack of requirement of DNA syn
like in maturing at the cell surface, it is not surprising that
thesis for antigen formation in the adenovirus lytic infection,
specific viral antigen, as well as tumor antigens, has been demon
and we have shown the same in the case of polyoma (Chart 2).
strated in the cell wall (36).
In our studies with polyoma, both FUDR and cytosine arabinoThis introduces the question of the nature of these antigens
side
showed the same results—an inhibition of production of
and their relationship to the virus itself. In the DNA tumor virus
systems, all the evidence is that neither type of new antigen is infectious virus and viral antigen but no inhibition of the tumor
CF antigen. We have also used ultraviolet irradiation-inactivated
present in the structure of the virus particle (8, 11). Furthermore,
polyoma virus to test whether intact DNA of the virus inoculum
in the case of polyoma and SV-40 tumors, the homotransplanta
is
required for T-antigen production, and apparently it is, since
tion antigen and the CF antigen appear to be separate and dis
no antigen was produced in cells inoculated with the inactivated
tinct entities in the same cell (11). Much more is known con
cerning the CF antigen because of the ease of quantitative
virus.
testing compared with the homotransplantation type.
In our hands, inhibitors of RNA and protein synthesis de
The reactions of the tumor-bearing and the virus-infected
creased the production of infectious virus, viral antigen, and
animals to the 2 types of antigens differ in the polyoma system.
T-antigen in the polyoma system. This was found with actinoWhereas the CF antigen calls forth a serum antibody, the trans
mycin D, mitomycin, and puromycin (see Charts 3-5). In the
plantation antigen produces a lymphocyte-mediated cellular
case of puromycin, when increasing amounts of inhibitors were
reaction such as is seen in graft rejection. Yet both reactions
used
there appeared to be a greater sensitivity to inhibitor on the
occur as the result of tumor inoculation. However, on inoculation
part
of
the synthetic apparatus for viral antigen than in that for
of the animal with virus, the transplant rejection response is
tumor
antigen.
Actinomycin and puromycin appeared to exert
consistently present, but the appearance of antibodies against
their
inhibitory
effect when added any time up to 12 hr after
the CF antigen is variable and is frequently absent unless the
infection in a system where the tumor antigen usually appeared
animal develops a tumor of its own. Occasionally CF antibodies
will appear and subsequently disappear, apparently, in response by 18 hr in infected control cultures.
to antigen produced by lytic viral multiplication in the mouse.
Two important difficulties have limited the inhibitor studies.
First, it is difficult to infect 100% of the cells in the polyoma
Formation of CF Tumor Antigen in Lytic Polyoma Infec
system, even with high multiplicities of infection; and secondly,
tion
the growth cycle is relatively so long that the inhibitors may
exert
a toxic effect on the cells before they are harvested for
When jjolyoma virus is used to infect secondary cultures of
mouse embryos, a lytic cycle of virus replication occurs with new- antigen titrations.
Present in tumor cells
Present in in vitro transformed cells
Present in lytic infection
Location in cell
Specificity
Cross-reacting between species
Animal reaction
Cell mediated
Serum antibody
Produced by virus inoculation
Produced by tumor inoculation
Involved in viral oncogenesis
SEPTEMBER 1966
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.
2019
Karl Hobel
o =VIRAL ANTIGEN CF
•= TUMOR ANTIGEN
CF
-
2
18 24 28
36
42 48
3+
CPE
CHART 1. Secondary
mouse embryo
4
cultures
inoculated
with polyoma
virus
(MOI = 100), adsorbed
times, and incubated in medium. Titers are for 0.2 ml of a 10% cell extract. The abbreviations
tion; PFU, plaque-forming units; MOI, multiplicity of infection; CPE, cytopathic effect.
used are:
3 hr at 37°C,washed
CF, complement
3
fixa
TABLE 2
SECONDARYHAMSTER EMBRYOCULTURES INOCULATEDWITH POLYOMAVIRUS (MOI = 100)"
Cultures were trypsinized and divided 2 to 1 at 60 days and 4 to 1 at 67, 74, and 80 days. CF results
are reciprocals of dilution of a 10% cell extract giving 3+ end points. PFU are the number of infectious
virus plaques formed by inoculating 0.2 ml of 10% cell extract onto mouse embryo cultures.
AVS POSTINTECTION
CFTumor
Virus
CFPFU
X IO602<113i16<124216<1931629516<1881612.812814.917410.424<420.2604266722174<1<180<1<10.03
MOI, multiplicity of infection; CF, complement-fixation; PFU, plaque-forming unit.
CF Tumor
Antigen
Production
in Transforming
Polyoma
System
When hamster embryo cultures are infected with polyoma
virus, only limited virus replication takes place with no apparent
cell destruction, and transformation occurs in up to 10% of the
cells (28, 32).
Preliminary experiments on the appearance of the T-antigen
in hamster embryo cultures infected with polyoma virus give a
somewhat different picture from that seen with mouse embryo
cultures. The CF antigen appears early, although not as early as
in the mouse embryo cultures, and persists in spite of only limited
viral replication.
In Table 2 are shown the results when secondary hamster
embryo cultures were inoculated with approximately 10 PFU
of polyoma virus per cell and the culture medium was changed
twice weekly without subdivision of the cultures for 60 days.
Both infectious virus and viral CF antigen persisted at low levels.
The tumor antigen was first demonstrable at 3 days and con
tinued at low levels. However, when these cultures were trypsi
2020
nized and divided 4 to 1 at weekly intervals, starting at 60 days,
there was a progressive drop in both types of CF antigen and
infectious virus.
In Table 3 a comparison can be made between the events in
the predominantly lytic virus cycle in mouse embryo cultures
and the nonlytic response of hamster embryo cultures. In the
lytic mouse embryo system viral multiplication was evidenced
by early and sharp increases in viral CF antigen and infectious
virus and by cytopathic effect on the cells, whereas the T-antigen
production was at its height at 1 day and not demonstrable at
6 days. Antigen and infectious virus production in the nonlytic
hamster culture was not found until the 2nd day, was quantita
tively low, and tended to persist at about the same levels. After
virus carrier cultures had teen established in both cell systems
at 22 days, there was not any marked difference between the 2.
It is of interest to compare the T-antigen levels in relation to the
amount of new virus production in the early stages of infection
in the 2 systems. For instance, at 2 days in the mouse cell cultures
there were 40 X IO6 PFU/CF unit of T-antigen, but in the
hamster system only 0.6 X IO6 PFU.
CANCER RESEARCH VOL. 26
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.
Virus Tumor Antigens
These results are consistent with the higher efficiency of virus
replication in the METC and of transformation in the HETC,
with T-antigen production accompanying both types of cell
response to infection. The previously demonstrated rapid appear
ance and subsequent loss of T-antigen during lytic infection and
its persistence at low levels in transforming infection can explain
these comparative results with the eventual similar findings in
CF
64
Pfu
xio6
80
Controls
|
FUDR
H
evi
m
32
¡6
40
20
10
Pfu
VIRUS
CF
30
TUMOR
CF
HR POST-INFECTION
CHART 2. Secondary mouse embryo tissue culture inoculated
with polyoma virus (MOI = 20). Inhibitors present during 3 hr
of virus adsorption and in medium after washing 3 times. FUDR
was used at 10~5 M and CYT at 10~3 5 M. The abbreviations used
are: CF, complement fixation; PFU, plaque-forming units; MOI,
multiplicity
of infection;
FUDR, 5-fluorodeoxyuridine;
and
CYT, cytosine arabinoside.
both systems on more prolonged culture. The findings are similar
to those obtained by Hoggan et al. (15) on shorter term culture
of adenovirus 12 in the lytic KB cell system versus the trans
forming hamster embryo culture.
Evidence that
Viral Genome
Antigens
Reflect
Message
Originating
in
Direct evidence is yet to be produced to establish that the
appearance of the 2 types of new antigen in cells transformed by
the DNA tumor viruses is due to protein formation coded by the
persisting viral genome. Yet a number of experimental facts
strongly suggest that this may be true, (a) The antigens are
virus specific, or where cross reactions occur with the serologie
antigens, there are other biologic characteristics in common
between the cross-reacting viruses. (6) The antigens occurring
in transformed cells and tumors of different histologie types and
even in different species appear to be immunologically the same.
(c) In the polyoma virus marker rescue experiments reported by
Ting (34), the genetic marker demonstrated in the virus progeny
produced after superinfection of a "virus-free" polyoma-transformed cell was associated with homotransplantation antigen
production, (d) Both types of antigen persist in tumors through
many transplant passages and in cells transformed in vitro
through multiple cell generations, both with RNA viruses where
continuation of virus replication can be readily demonstrated
and with DXA viruses where infectious virus disappears, (è)
In the non-virus-producing Rous tumor cells induced in mam
mals, which are analogous to tumors induced by DNA viruses,
the CF antigen persists and infectious virus can again be demon
strated when the tumors are transferred to chickens. (/) It has
been shown that a single mouse embryo culture cell already
morphologically transformed by 1 DNA tumor virus (polyoma)
can be "supertransformed" by a 2nd DNA tumor virus (SV-40).
The doubly transformed cells contain the specific C'F tumor
antigens for both viruses (to be published by G. .1. Todaro, K.
Habel, and H. Green). Likewise, a hamster SV-40 tumor cell
has been "supertransformed" by infection with polyoma virus
with the production of T-antigens for both (to be published bv
K. K. Takemoto and K. Habel).
TABLE 3
SECONDARY
MOUSEANDHAMSTEREMBRYOCULTURESINOCULATED
WITHPOLYOMA
VIRUS (MOI = 10)"
POSTINFECTION0<1<10.40112.4018107.60112.7026483202+885.1046423+821106128<111002+02242201+3223.10
CUI/TUREMouse
embryoHamster
CF°Tumor
CFPFU
IO6CPEViral
X
embryoTESTViral
CFTumor
CFPFU
10"CPEDAYS
X
•
MOI, multiplicity
pathic effect.
SEPTEMBER
1966
of infection;
CF, complement
fixation; PFU, plaque-forming
units; CPE, cyto-
2021
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.
Karl Hobel
Implications
Oncogenirity
of
Virus-induced
Tumor
Antigens
for
That the new Homotransplantation type of antigen produced
in polyoma virus-induced tumor cells and the animal's immuno
logie reaction to it are important determinants of tumor produc
tion is now well established (8,10). The hypothesized mechanism
is as follows. When the virus transforms normal cells to tumor
cells in vivo, these cells contain the new foreign antigen to which
the immunologically competent normal adult animal reacts,
rejecting the tumor cells in a homograft reaction and thus pre-
fj.q OF ACTINOMYCIN
D
CF
150
8
1
OJ
0§
75
5C
'Ao.o.i.
VIRUS
CF
THYMIDINE-3H
TUMOR
CF
27 HR
UPTAKE
POST
VALINE-I4C
UPTAKE
INFECTION
CHART3. Secondary mouse embryo tissue culture inoculated with polyoma virus (MOI = 100).Actinomycin D present from 0 time
Figures at tops of columns give ¿ig
of inhibitor per ml. Uptake of labeled precursors is expressed as % of that in infected control culture.
Cell extract TCA precipitated before and after DNase treatment and counted in scintillation counter. The abbreviations used are MOI,
multiplicity of infection; CF, Complement fixation; and TCA, trichloracetic acid.
10
THYMIDINE-3H
VALINE-I4C
27
HR
POST
-
50
-
25
UPTAKE
INFECTION
CHART4. Secondary mouse embryo tissue culture inoculated with polyoma virus (MOI = 100). Mitomycin C was present from 0
time until time of harvest at 27 hr. The concentration of inhibitor in ¿ig/mlis given above each column. The uptakes of labeled precur
sors into DNA and protein were proportionately so similar that they are plotted together. The abbreviations used are: MOI, multi
plicity of infection; CF, complement fixation; and PFU, plaque-forming units.
2022
CANCER RESEARCH VOL. 26
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.
Virus Tumor Antigens
CF
32
16
0
fj.q OF
inhibition, cell division, intercellular exchange of materials and
immunologie reactions, the significance of these antigens to
oncogenesis may be found greater than is now apparent.
PUROMYCIN
l
%
100
l
Ü
1.0
0
10
80
60
W//
30
40
20
3.0
3.0.
VIRUS
TUMOR
THYMIDINE-JH
VALINE-14C
CF
CF
UPTAKE
UPTAKE
29
HR
POST
INFECTION
CHART5. Secondary mouse embryo tissue culture inoculated
with polyoma virus (MOI = 100). Puromycin was present from 0
time. Figures at the tops of columns show /ig of inhibitor per ml.
The abbreviations used are: MOI, multiplicity of infection; and
CF, complement fixation.
venting gross tumor production and rendering the animal immune
to later tumor challenge. When this same transformation takes
place in an immunologically immature newborn or an adult
made immunologically incompetent by early thymectomy (21)
or whole-body X-irradiation (20), gross tumors do develop.
There is good reason to believe that this immunologie mecha
nism explains the extreme rarity of polyoma-induced tumors in
mouse colonies heavily infected under natural conditions of
exposure. However, Law (19) has shown that under these condi
tions of natural exposure thymectomized mice do indeed develop
spontaneous polyoma tumors.
There is as yet no evidence that the CF antigen in DNA virustransformed cells is responsible for the tumor properties of the
cell or influences tumor development in the animal. The results
of experiments demonstrating its early appearance in lytic virus
infection would suggest by analogy with other lytic virus systems
that this antigen may represent an early enzyme required for
some stage of virus replication. Its demonstrated persistence in
the transformed cell in spite of no production of complete in
fectious virus suggests that it may be required for the replication
of that part of the viral genome which may be integrated into
the cell genome.
In the case of UNA virus-transformed cells where the viral
antigens are present in the cell wall, and especially in leukemias
where lysis of cells can be accomplished by cytotoxic antibodies
against new cell wall antigens, it is certainly possible that the
serologie antigens and antibodies to them may help control
tumor development.
Since both types of the new tumor antigens can occur in the
cell surface of certain virus-induced tumors and since the cell
membrane is obviously important in such phenomena as contact
References
Armstrong, D., Okuyan, M., and Huebner, R. J. Complementfixing Antigens in Tissue Cultures of Avian Leukosis Viruses.
Science, 144: 1584, 1964.
Axelrod, D., Habel, K., and Bolton, E. T. Polyoma Genetic
Material in a Virus-free Polyoma Induced Tumor. Ibid.,
146: 1466-09, 1964.
Bases, II. Antigenic Differences between Normal and Polyoma
Virus-transformed Cells. II. In vitro Evidence for a Virusinduced Antigen. Cancer Res., 24: 1216-21, 1964.
Gerber, P. Virogenic Hamster Tumor Cells : Induction of Virus
Synthesis. Science, 145: 833, 1964.
Gilead, Z., and Ginsberg, H. S. Characterization of a Tumorlike Antigen in Type 12and Type 18Adenovirus Infected Cells.
J. Bacterio!., 90: 120-25, 1965.
Girardi, A. J. Prevention of SV 40 Virus Oncogenesis in Ham
sters. I. Tumor Resistance Induced by Human Cells Trans
formed by SV 40. Proc. Nati. Acad. Sci., U.S., 54: 445-51, 1965.
Habel, K. Resistance of Polyoma Virus Immune Animals to
Transplanted Polyoma Tumors. Proc. Soc. Expt!. Biol. Med.,
106: 722-25, 1961.
—.Immunologie-ai Determinants of Polyoma Virus Onco
genesis. J. Exptl. Med., 115: 181-93, 1962.
Polyoma Tumor Antigen in Cells Transformed in
9.
vitro by Polyoma Virus. Virology, 18: 553-58, 1962.
—.The Relationship between Polyoma Virus Multiplica
10.
tion, Immunologioal Competence, and Resistance to Tumor
Challenge in the Mouse. Ann. N. Y. Acad. Sci., 101: 173-79,
1962.
11. —- . Specific Complement-fixing Antigens in Polyoma
Tumors and Transformed Cells. Virology, 25: 55-61, 1965.
12. Habel, K., and Eddy, B. E. Specificity of Resistance to Tumor
Challenge of Polyoma and SV 40 Virus-immune Hamsters.
Proc. Soc. Exptl. Biol. Med., 113:1-12, 1963.
13. Habel, K., Jensen, F., Pangan»,J. S., and Koprowski, H.
Specific Complement-fixing Tumor Antigen in SV 40 Trans
formed Human Cells. Ibid., 118: 4-9, 1965.
14. Hartley, J. W., Rowe, W. P., Capps, W. I., and Huebner, R.
J. Complement-fixation and Tissue Culture Assays for Mouse
Leukemia Viruses. Proc. Nat!. Acad. Sci., U.S., 53: 931-38,
1965.
15. Hoggan, M. D., Rowe, W. P., Black, P. H., and Huebner, R.
J. Production of "Tumor-specific" Antigens by Oncogenic
Viruses during Acute Cytolytic Infections. Ibid., S3: 12-19,
1965.
16. Huebner, R. J., Rowe, W. P., Turner, H. C., and Lane, W. T.
Specific Adenovirus Complement-fixing Antigens in Virusfree Hamster and Rat Tumors. Ibid., 50: 379-89, 1963.
17. Ito, Y. A Tumor-producing Factor Extracted by Phenol from
Papillomatous Tissue (Shope) of Cottontail Rabbits. Virology,
/a: 596-601, 1960.
18. Klein, E., and Klein, G. Antigenic Properties of Lymplioina.s
Induced by the Moloney Agent. J. Nati. Cancer Inst., SS:
547-68, 1964.
19. Law, L. W. Neoplasms in Thymectomized Mice following
Room Infection with Polyoma Virus. Nature, 205: 672-73, 1965.
20. Law, L. W., and Dawe, C. J. Influence of Total Body X-irradi
ation on Tumor Induction by Parotid Tumor Agent in Adult
Mice. Proc. Soc. Exptl. Biol. Med., 105: 414-19, 1960.
SEPTEMBER 1966
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.
2023
Karl Habd
to Polyoma-virus-induced Tumors. III. Transplantation
21. Malmgren, R. A., Rabson, A. S., and Carney, P. G. Immunity
and Viral Carcinogenesis. Effect of Thymectomy on Polyoma
Resistance to Genetically Compatible Polyoma Tumors In
Virus Carcinogenesis in Mice. J. Nati. Cancer Inst., 33: 101-4,
duced by Polyoma Tumor Homografts. J. Nati. Cancer Inst.,
23: 645-66, 1964.
1964.
22. Old, L. J., Boyse, E. A., and Lilly, F. Formation of Cytotoxic
30. Sjögren,H. O., Hellström,L, and Klein, G. Transplantation
of Polyoma Virus Induced Tumors in Mice. Cancer Res., 21:
Antibody against Leukemias Induced by Friend Virus. Can
329-37, 1961.
cer Res., 23: 1063-C8,1963.
23. Old, L. J., Boyse, E. A., and Stockert, E. Typing of Mouse 31. Slettenmark, B., and Klein, E. Cytotoxic and Neutralization
Leukemias by Serological Methods. Nature, 201: 201-2, 1904.
Tests with Serum and Lymph Node Cells of Isologous Mice
with Induced Resistance against Gross Lymphomas. Ibid.,
24. Pope, J. H., and Rmve, W. P. Detection of Specific Antigen in
22: 947-54, 1962.
SV 40 Transformed Cells by Immunofluorescence. J. Exptl.
Med., 120: 121-27, 1964.
32. Stoker, M., and Macpherson, I. Studies on Transformation of
Hamster Cells by Polyoma Virus in vitro. Virology, 14: 35925. Rapp, F., Butel, J. S., Feldman, L. A., Kitahara, T., and Melnick, J. L. Differential Effects of Inhibitors on the Steps Lead
70, 1961.
ing to the Formation of SV 40 Tumor and Virus Antigens. 33. Tevethia, S. S., Katz, M., and Rapp, F. New Surface Antigen
Ibid., 121: 935-44, 1905.
in Cells Transformed by Simian Papovavirus SV 40. Proc.
Soc. Exptl. Biol. Med., 119: 896-901, 1965.
26. Rapp, F., Kitahara, T., Butel, J. S., andMelnick, J. L. Synthe
sis of SV 40 Tumor Antigen during Replication of Simian 34. Ting, R. C. A New Approach for the Demonstration of Viral
Papovavirus (SV 40). Proc. Xatl. Acad. Sci., U.S., 52: 1138-42,
Genes in Virus-free Polyoma Tumor Cells. Virology, 24:
227-28, 1964.
1904.
35. Vogt, M., and Dulbecco, R. Virus-cell Interaction with a
27. Sabin, A. B., and Koch, M. A. Source of Genetic Information
Tumor-producing Virus. Proc. Nati. Acad. Sci., U.S., #?:
for Specific Complement-fixing Antigens in SV 40 Virusinduced Tumors. Ibid., 52: 1131-38, 1964.
305-70, 1960.
28. Sachs, L., Medina, IX, and Berwald, Y. Cell Transformation
36. Vogt, P. K., and Rubin, H. Localization of Infectious Virus
by Polyoma Virus in Clones of Hamster and Mouse Cells.
and Viral Antigen in Chick Fibroblasts during Successive
Virology, 17: 491-93, 1962.
Stages of Infection with Rous Sarcoma Virus. Virology, IS:
528-44,1961.
29. Sjögren,H. O. Studies on Specific Transplantation Resistance
2024
CANCER RESEARCH VOL. 26
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.
Virus Tumor Antigens: Specific Fingerprints?
Karl Habel
Cancer Res 1966;26:2018-2024.
Updated version
E-mail alerts
Reprints and
Subscriptions
Permissions
Access the most recent version of this article at:
http://cancerres.aacrjournals.org/content/26/9_Part_1/2018
Sign up to receive free email-alerts related to this article or journal.
To order reprints of this article or to subscribe to the journal, contact the AACR Publications
Department at [email protected].
To request permission to re-use all or part of this article, contact the AACR Publications
Department at [email protected].
Downloaded from cancerres.aacrjournals.org on June 18, 2017. © 1966 American Association for Cancer Research.