Levels Of Tumor Antigen Research Articles

Immuno-PET Imaging and Radioimmunotherapy of Lymphomas.

Monoclonal antibodies (Ab) have revolutionized the management of lymphomas, the most common hematologic malignancy in adults. Indeed, incorporation of rituximab into the regimen for indolent non-Hodgkin's lymphomas (NHLs) has dramatically improved treatment response and disease outcome. Yet, newer Ab therapeutics against promising antigen targets need to be developed to treat refractory or relapsed patients. Treatment efficacy can be further enhanced by conjugating toxic molecules to the Abs. Radioimmunotherapy (RIT) harnesses Abs as vehicles for targeted delivery of therapeutic radionuclide payloads for direct killing of targeted tumor cells. Positron emission tomography (PET) with radiolabeled Abs (called immuno-PET) can facilitate the development of new Ab therapeutics and RIT by providing pharmacokinetic and pharmacodynamic information and by quantifying tumor antigen level relevant for treatment decision. Immuno-PET has recently gravitated toward labeling Abs with 89Zr, a radiometal with a 3.3 day half-life that is trapped following Ab internalization and thus provides high-resolution PET images with excellent contrast. Immuno-PET methods against major lymphoma antigens including CD20 and other promising targets are currently under development. With continued improvements, immuno-PET has the potential to be used in lymphoma management as an imaging biomarker for patient selection and assessment of treatment response.

Cellular Immunotherapies for Leukemia Patients

Cellular Immunotherapies for Leukemia Patients

PET-based compartmental modeling of (124)I-A33 antibody: quantitative characterization of patient-specific tumor targeting in colorectal cancer.

The molecular specificity of monoclonal antibodies (mAbs) directed against tumor antigens has proven effective for targeted therapy of human cancers, as shown by a growing list of successful antibody-based drug products. We describe a novel, nonlinear compartmental model using PET-derived data to determine the "best-fit" parameters and model-derived quantities for optimizing biodistribution of intravenously injected (124)I-labeled antitumor antibodies. As an example of this paradigm, quantitative image and kinetic analyses of anti-A33 humanized mAb (also known as "A33") were performed in 11 colorectal cancer patients. Serial whole-body PET scans of (124)I-labeled A33 and blood samples were acquired and the resulting tissue time-activity data for each patient were fit to a nonlinear compartmental model using the SAAM II computer code. Excellent agreement was observed between fitted and measured parameters of tumor uptake, "off-target" uptake in bowel mucosa, blood clearance, tumor antigen levels, and percent antigen occupancy. This approach should be generally applicable to antibody-antigen systems in human tumors for which the masses of antigen-expressing tumor and of normal tissues can be estimated and for which antibody kinetics can be measured with PET. Ultimately, based on each patient's resulting "best-fit" nonlinear model, a patient-specific optimum mAb dose (in micromoles, for example) may be derived.

Trojan T cell horse: TLR5 ligand-secreting T cells reshape the tumor microenvironment and exhibit enhanced antitumor activity (TUM2P.909)

Abstract T cell responses are downregulated by the immunosuppressive tumor microenvironment. On the basis of previous studies demonstrating that Toll-like receptor (TLR) engagement on T cells augments their responses, we hypothesized that T cells engineered to secrete the TLR5 ligand flagellin would enhance T cell costimulation in the tumor environment and augment antitumor activity. Human T cells engineered to express the MART-1 TCR and secrete TLR5-ligand (TLR5-L) responded to lower tumor antigen levels resulting in increased proliferation, cytolytic activity and reversed tumor growth associated with prolonged mouse survival in a xenogeneic model. Treatment with TLR5-L-secreting T cells eradicated tumor in 40% of mice in a syngeneic model. Intratumoral secretion of TLR5-L by T cells reshaped the tumor microenvironment in part by inducing of a distinct chemokine/cytokine profile rendering it more immunogenic and permissive to T cell infiltration. Furthermore, tumor lysis by TLR5-L-producing T cells triggered the priming of endogenous tumor-reactive CD8 and CD4 T cells. Characterization of the cellular composition of the tumor and spleen revealed a reduction in MDSCs in the spleen and increased expression of MHC I in the tumor. This study demonstrates for the first time the ability to use T cells to deliver a TLR agonist to the tumor site and that intratumoral TLR5-L contributes to various processes involved in tumor regression.

Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients.

BackgroundAscorbic acid (vitamin C, ascorbate) is a key water soluble antioxidant that, when administered in doses well above its recommended dietary allowance, may have preventative and therapeutic value against a number of pathologies. The intravenous administration of high dose ascorbate (IVC) has increased in popularity among complementary and alternative medicine practitioners: thousands of patients received IVC, at an average dose of 0.5 g/kg, without significant side effects. While IVC may have a variety of possible applications, it has generated the most interest for its potential use in treating cancer.MethodsMedical records of patients with cancer treated with IVC at the Riordan Clinic were retrospectively reviewed. Cancer patients, for whom plasma ascorbate concentration data before and after treatment were available, along with C-reactive protein (CRP) measurements, were chosen for analysis.ResultsThe results of the analysis can be summarized as follows. IVC produces peak plasma ascorbate concentrations on the order of ten millimolars with lower peak plasma concentrations obtained in cancer patients as compared to healthy subjects. Cancer patients who are deficient in vitamin C prior to therapy tend to achieve lower plasma levels post infusion. High inflammation or tumor burdens, as measured by CRP or tumor antigen levels, tend to lower peak plasma ascorbate levels after IVC. When compared to patients with localized tumors, patients with metastatic tumors tend to achieve lower post infusion plasma ascorbate concentrations.ConclusionsThe data indicate that, while potentially therapeutic plasma ascorbate concentrations can be achieved with IVC, levels attained will vary based on tumor burden and degree of inflammation (among other factors). Evidence suggests that IVC may be able to modulate inflammation, which in turn might improve outcomes for cancer patients. IVC may serve as a safe, adjunctive therapy in clinical cancer care.

Modeling the CD8+ T Effector to Memory Transition in Adoptive T-Cell Antitumor Immunotherapy

Adoptive T-cell therapy with CD8(+) CTLs is often characterized by poor persistence of the transferred T cells and limited effector responses. Improved persistence and therapeutic efficacy have been noted when antigen-activated CD8(+) T cells express properties of memory cells. The current study was undertaken to more precisely characterize the development of memory-like CD8(+) T cells from short-term CTLs in vitro and upon transfer in vivo, including their antitumor activity. Ovalbumin (OVA)-specific OT-I CTLs acquired phenotypic and functional properties of memory cells 2 to 3 days later either by lowering the concentration of antigen to a level that does not support primary responses and providing a survival signal through transgenic Bcl-2 in vitro or simply by transferring early day 3 CTLs to antigen-free lymphoid-replete mice. In lymphoid-replete mice, established OVA-expressing E.G7 tumor was rejected by short-term CTLs that simultaneously acquired memory-like properties in secondary lymphoid tissues, where tumor antigen level remained low. Collectively, these data indicate that CTLs readily converted to memory-like cells upon lowering antigen to a concentration that selectively supports memory responses and suggest that such conversion predicts successful adoptive immunotherapy.

Differential capacity of chaperone-rich lysates in cross-presenting human endogenous and exogenous melanoma differentiation antigens

The goal of immune-based tumor therapies is the activation of immune cells reactive against a broad spectrum of tumor-expressed antigens. Vaccines based on chaperone proteins appear promising as these proteins naturally exist as complexes with various protein fragments including those derived from tumor-associated antigens. Multi-chaperone systems are expected to have highest polyvalency as different chaperones can carry distinct sets of antigenic fragments. A free-solution isoelectric focusing (FS-IEF) technique was established to generate chaperone-rich cell lysates (CRCL). Results from murine systems support the contention that CRCL induce superior anti-tumor responses than single chaperone vaccines. We established an in vitro model for human melanoma to evaluate the capacity of CRCL to transfer endogenously expressed tumor antigens to the cross-presentation pathway of dendritic cells (DC) for antigen-specific T cell stimulation. CRCL prepared from human melanoma lines contained the four major chaperone proteins Hsp/Hsc70, Hsp90, Grp94/gp96 and calreticulin. The chaperones within the melanoma cell-derived CRCL were functionally active in that they enhanced cross-presentation of exogenous peptides mixed into the CRCL preparation. Superior activity was observed for Hsp70-rich CRCL obtained from heat-stressed melanoma cells. Despite the presence of active chaperones, melanoma cell-derived CRCL failed to transfer endogenously expressed melanoma-associated antigens to DC for cross-presentation and cytotoxic T cell (CTL) recognition, even after increasing intracellular protein levels of tumor antigen or chaperones. These findings reveal limitations of the CRCL approach regarding cross-presentation of endogenously expressed melanoma-associated antigens. Yet, CRCL may be utilized as vehicles to enhance the delivery of exogenous antigens for DC-mediated cross-presentation and T cell stimulation.

Oncolytic Immunovirotherapy for Melanoma Using Vesicular Stomatitis Virus

Relatively little attention has been paid to the role of virotherapy in promoting antitumor immune responses. Here, we show that CD8+ T cells are critical for the efficacy of intratumoral vesicular stomatitis virus virotherapy and are induced against both virally encoded and tumor-associated immunodominant epitopes. We tested three separate immune interventions to increase the frequency/activity of activated antitumoral T cells. Depletion of Treg had a negative therapeutic effect because it relieved suppression of the antiviral immune response, leading to early viral clearance. In contrast, increasing the circulating levels of tumor antigen-specific T cells using adoptive T cell transfer therapy, in combination with intratumoral virotherapy, generated significantly improved therapy over either adoptive therapy or virotherapy alone. Moreover, the incorporation of a tumor-associated antigen within the oncolytic vesicular stomatitis virus increased the levels of activation of naïve T cells against the antigen, which translated into increased antitumor therapy. Therefore, our results show that strategies which enhance immune activation against tumor-associated antigens can also be used to enhance the efficacy of virotherapy.

Differential effects of c-Ras upon transformation, adipocytic differentiation, and apoptosis mediated by the simian virus 40 large tumor antigen

To investigate the functional relationship between the ability of the simian virus 40 large tumor antigen (TAg) to transform and its ability to block adipocytic differentiation and induce apoptosis, we expressed TAg in C3H10T1/2 (10T1/2)-derived preadipocytes. The results demonstrated that differentiation could be suppressed at lower TAg levels than at the levels required for full neoplastic conversion. Progressively higher TAg levels were accompanied by apoptosis induction in this system. To further examine the role of the cellular Ras protooncogene product (Ras) in TAg function, TAg was expressed in 10T1/2-derived preadipocytes rendered deficient in Ras activity by transfection with inducible or constitutive antisense ras gene constructs. The results indicated that Ras is required for TAg-mediated transformation and for suppression of adipocytic differentiation, while TAg-mediated apoptosis following serum starvation was independent from Ras action. Unexpectedly, our results further demonstrated a dramatic reduction in the levels of the TAg protein itself as differentiation progressed in Ras-knockdown cells, with a concomitant reduction in TAg's ability to induce apoptosis as a result. These findings suggest that Ras, although cytoplasmic, is an integral component of the pathway whereby TAg, an oncoprotein believed to have primarily nuclear targets, suppresses differentiation or induces neoplastic conversion of murine preadipocytes.

Intralymphatic Dendritic Cell Vaccination Induces Tumor Antigen–Specific, Skin-Homing T Lymphocytes

The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen-specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen-specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are "imprinted" in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.

Localization of Transgenes and Genotyping of H-2K b -tsA58 Transgenic Mice

Localization of Transgenes and Genotyping of <i>H-2K</i> ^b -tsA58 Transgenic Mice

Limited prognostic value of c-erbB-2 compared to uPA and PAI-1 in primary breast carcinoma.

In a retrospective study of 488 women with primary breast cancer, after a median follow-up of 10 years, we sought interactions between disease-free survival (DFS) and overall survival (OS) and tumor antigen levels of two components of the plasminogen system, urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and the transmembrane growth factor receptor c-erbB-2. We used ELISAs (American Diagnostica, Greenwich, CT, USA) to quantify uPA and PAI-1 antigen levels in cytosols, and a double monoclonal antibody-based assay (EIA) (Ciba Corning Diagnostics, Alameda, CA, USA) to quantify c-erbB-2 in membrane extracts of the same tissues. Weak positive correlations were found between uPA and c-erbB-2 (r(s) = 0.146; p = 0.001) and between PAI-1 and c-erbB-2 (r(s) = 0.154; p < 0.001). In the overall population, using univariate analyses, c-erbB-2 overexpression and high uPA and PAI-1 antigen levels (> 300 IU/mg, > 1.40 ng/mg and > 5.53 ng/mg, respectively) were significantly associated with shorter DFS (p = 0.003, p < 0.001 and p < 0.001, respectively) and OS (p < 0.001 in all cases). Using multivariate analyses, PAI-1, node status and tumor size were independent predictors of DFS and c-erbB-2 was retained in the model only for OS. In the node-negative subgroup, PAI-1 was the strongest significant survival predictor both for OS (p = 0.003; HR 2.52) and DFS (p < 0.001; HR 2.39). This study shows that in primary breast cancer c-erbB-2 offers no additional prognostic information when uPA and/or PAI-1 are candidates in the multivariate analyses.

Limited prognostic value of c-erbB-2 compared to uPA and PAI-1 in primary breast carcinoma

In a retrospective study of 488 women with primary breast cancer, after a median follow-up of 10 years, we sought interactions between disease-free survival (DFS) and overall survival (OS) and tumor antigen levels of two components of the plasminogen system, urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and the transmembrane growth factor receptor c-erbB-2. We used ELISAs (American Diagnostica, Greenwich, CT, USA) to quantify uPA and PAI-1 antigen levels in cytosols, and a double monoclonal antibody-based assay (EIA) (Ciba Corning Diagnostics, Alameda, CA, USA) to quantify c-erbB-2 in membrane extracts of the same tissues. Weak positive correlations were found between uPA and c-erbB-2 (r(s) = 0.146; p = 0.001) and between PAI-1 and c-erbB-2 (r(s) = 0.154; p < 0.001). In the overall population, using univariate analyses, c-erbB-2 overexpression and high uPA and PAI-1 antigen levels (> 300 IU/mg, > 1.40 ng/mg and > 5.53 ng/mg, respectively) were significantly associated with shorter DFS (p = 0.003, p < 0.001 and p < 0.001, respectively) and OS (p < 0.001 in all cases). Using multivariate analyses, PAI-1, node status and tumor size were independent predictors of DFS and c-erbB-2 was retained in the model only for OS. In the node-negative subgroup, PAI-1 was the strongest significant survival predictor both for OS (p = 0.003; HR 2.52) and DFS (p < 0.001; HR 2.39). This study shows that in primary breast cancer c-erbB-2 offers no additional prognostic information when uPA and/or PAI-1 are candidates in the multivariate analyses.

Prolonged Symptom-Free Survival in a Patient with Persistent Primary Peritoneal Carcinoma and a Rising CA-125: A Note of Caution

Background. The optimal management of patients with ovarian and primary peritoneal carcinomas who experience an elevation of the serum CA-125 antigen level following the completion of therapy, and who remain without other clinical evidence of recurrent/progressive disease, remains controversial.Case. A patient with primary peritoneal carcinoma cared for in the Gynecologic Cancer Program of the Cleveland Clinic Foundation has experienced prolonged symptom-free survival (>4 years) after a documented tripling of her persistently elevated postchemotherapy serum CA-125 without the reinstitution of cytotoxic therapy.Conclusion. This case emphasizes that caution must be exercised when electing to initiate second-line treatment solely on the basis of an abnormal tumor antigen level.

Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy.

Patients with metastatic breast, colorectal or ovarian cancers received active specific immunotherapy (ASI) with Theratope sialyl-Tn-KLH (keyhole limpet hemocyanin) cancer vaccine emulsified in Detox adjuvant. The median log2 anti-STn IgG titer generated by ASI, estimated by enzyme-linked immunosorbent assay with solid-phase ovine submaxillary mucin, was 5.322 (range = 0 - 9.322). Following ASI, 51 patients who generated titers higher than the median value for anti-STn+ mucin IgG survived longer than 46 patients who generated lower titers below the median. 38 of the patients were phenotyped for CD69 prior to ASI. The patients with lower numbers of CD69+ peripheral blood lymphocytes prior to immunotherapy (pre-ASI) also had low serum CA27.29 cancer antigen (MUC-1) levels, and had longer times to disease progression and improved survival following ASI. Elevated pre-ASI serum CA27.29 tumor antigen levels were associated with higher numbers of CD69+ PBL, with decreased anti-STn antibody production and decreased survival following ASI. The data are compatible with the hypothesis that elevated serum MUC-1 mucin is specifically immunosuppressive.

Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen.

The ability of interferons (IFNs) to enhance tumor-associated antigen expression may be an important approach to enhance the efficacy of some monoclonal antibody (MAb)-based protocols for tumor diagnosis and/or therapy. The present study was designed to determine whether systemic IFN alpha-2a administration (via the intramuscular [IM] route) could upregulate the expression of tumor-associated glycoprotein-72 (TAG-72) and/or carcinoembryonic antigen (CEA) at histologically confirmed sites of carcinoma. Eighteen patients diagnosed with gastrointestinal (GI) carcinoma received systemic IFN alpha-2a according to four dose schedules. In cohorts I and II, patients received two injections of 3 or 6 x 10(6) U IFN alpha-2a per injection, respectively. Patients in cohorts III and IV received the same doses of IFN alpha-2a, 3 and 6 x 10(6) U, respectively, but three injections were given. Tumor and normal colonic mucosa biopsies were obtained from each patient by endoscopy before IFN alpha-2a and after IFN alpha-2a at surgery. The levels of TAG-72 and CEA expression were measured by (1) immunohistochemistry and reported as percent antigen-positive tumor cells, as well as the relative staining intensity, and (2) a quantitative radioimmunoassay. TAG-72 and CEA levels were consistently increased in tumor biopsies taken from patients in cohorts III and IV. For example, of 10 patients treated in cohorts III and IV, eight had enhanced TAG-72 expression when measured either as percentage TAG-72-positive tumor cells or as an increased MAb staining intensity following IFN alpha-2a. CEA expression in tumor biopsies from seven of 10 patients in cohorts III and IV was also elevated following IFN alpha-2a treatment. Quantitative analysis of TAG-72 and CEA levels in tumor biopsies confirmed higher tumor antigen levels following IFN alpha-2a administration. No such increases in TAG-72 or CEA levels were observed in tumor samples taken from patients in cohorts I and II. CEA or TAG-72 expression in samples of histologically confirmed normal colonic mucosa showed little or no change after IFN alpha-2a treatment. Systemic IFN alpha-2a administration can upregulate TAG-72 and CEA expression at distal tumor sites, which may play an important role in immunodiagnosis and therapy.

Tumor size, leukocyte adherence inhibition and serum levels of tumor antigen in dogs with the canine transmissible venereal sarcoma.

Tumor antigen (TA) associated with the canine transmissible venereal sarcoma (CTVS) was detected in the sera of dogs bearing the tumor. Rabbit antisera specific for tumor antigen and 3 M KCl extracts of CTVS cells were used in both a competitive enzyme-linked immunosorbent assay (ELISA) and antigen-capture ELISA to quantify levels of circulating TA. In a study of 29 dogs bearing the transplanted CTVS, levels of circulating TA correlated positively with tumor volume. In a longitudinal study of four dogs receiving a transplant of 10(8) viable CTVS cells, circulating CTVS antigen was detected transiently 2 days after transplantation, while persistent levels of TA associated with increasing tumor volume were demonstrable 19-34 days after transplantation. In three of four tumor-bearing dogs, levels of serum TA correlated inversely with values obtained with peripheral blood leukocytes in the leukocyte adherence inhibition (LAI) assay; elevated levels of circulating TA found in dogs with large (greater than 7 cm3) tumors were associated with decreased LAI reactivity of peripheral blood leukocytes. TA could not be detected in sera 48-72 h after surgical removal of CTVS whereas LAI reactivity of peripheral blood leukocytes to CTVS antigen rebounded 1-3 weeks following tumor excision. Results of this study support the use of the competitive ELISA and LAI techniques in assessing levels of circulating tumor antigen, tumor burden and tumor-specific immunity.

Role of respiratory-burst products from polymorphonuclear leukocytes in the antitumor activity of Propionibacterium acnes vaccine.

Tumor cells injected into Balb/c mice together with heat-killed 48-h P. acnes cells were rendered nontumorigenic as early as 12 h after injection, as determined by the inability of the tumor cells to give rise to tumors when transferred to a new host. Determination of tumor cell antigen levels by ELISA indicated that the tumour antigens had virtually disappeared by 24 h after injection of tumor cells and P. acnes. In contrast, in control animals injected with tumor cells only, there was an initial drop in tumor antigen levels at 12 h, after which the level rose steadily and tumors developed in 7-10 days. Since the cellular exudate at 12 h was almost entirely composed of polymorphonuclear leukocytes (PMN), we tested the ability of PMN, stimulated by phagocytosis of 48-h P. acnes cells, to produce substances toxic to tumor cells. Results indicated that the supernatant fluid from a phagocytosis mixture of PMN and P. acnes contained material toxic to tumor cells and also to Chinese hamster ovary cells. Tests with scavengers and inhibitors of oxygen-derived radicals suggested that the toxic material is either hydrogen peroxide (H2O2) or hydroxyl radicals (OH). Suspensions of 12-h P. acnes, P. acnes cells walls, P. freudenreichii, or latex beads were ineffective in preventing tumor growth, and induced little toxicity when phagocytosed. We conclude that in this test system 48-h P. acnes prevents tumor growth by stimulating the production of toxic oxygen metabolites during phagocytosis by PMN.

Squamous cell carcinoma antigen in patients with cancer of the uterine cervix.

The serum concentrations of the tumor-associated antigen SCC were determined in 62 patients with invasive carcinoma of the uterine cervix. Antigen values above 2.0 ng/ml were considered as slightly positive, and those above 4.0 ng/ml as highly positive. Pretherapeutic levels were elevated (greater than 2.0 ng/ml) in 68% of the patients with cervical carcinoma. In 49 patients with carcinoma in situ, 18% of the SCC values were above the normal range. The greatest incidence of positive SCC titers (84%) was observed in women with recurrent cervical carcinoma. Only 6.7% of women in remission had elevated titers. Five of 24 cases (21%) with invasive endometrial carcinoma had SCC values exceeding 2.0 ng/ml. Slightly positive levels of tumor antigen were seen in 1.8% (1/56) of the control subjects. Serial SCC determinations revealed a correlation with the clinical course of disease in 84%. The determination of SCC is useful for the surveillance of patients with cervical squamous cell carcinoma.

Relationship between simian virus 40 large tumor antigen expression and tumor formation in transgenic mice.

A line of transgenic mice containing the simian virus 40 (SV40) large tumor antigen gene under the control of the viral enhancer-promoter expressed this viral protein in the brains of these mice within the first 2 weeks after birth. Multiple foci of anaplastic cells formed in the choroid plexuses of these mice at 36 to 41 days after birth, and normal tissue coexisted with these transformed foci. Immunoperoxidase staining to detect the SV40 T antigen showed tumor-specific expression of nuclear T antigen at late times in tumor development, approximately 90 to 100 days and thereafter. The level of SV40 T antigen, on a per cell basis, appeared to be lower in the great majority of choroid plexus cells at earlier times in tumor development. These results suggest that low levels of tumor antigen (14 to 36 days) are present before detectable pathology (36 to 41 days) and the level of T antigen per cell is higher in rapidly growing late-stage tumors (older than 90 days).