Theratope

Vaccines generally used sialylated (s)Tn, which are mucin epitopes expressed on epithelial tumors, conjugated with KLH. This vaccine was commercialized as Theratope (Biomira Inc., Edmonton, Canada). In a phase I study O Boyle et al. [199] injected the vaccine to colorectal cancer patients. Toxicity was only local, and an antibody response was observed. 

Theratope was given to patients with breast or ovarian cancer who received peripheral blood stem cell rescue after chemotherapy. Toxicity was mostly local. In vitro, NK activity which was low before immunization returned to normal values, toxicity against cells bearing sTn antigen appeared, and lymphocytes responded to sTn, by proliferation and IFN-y production. Antibodies against sTn were detected in 16 patients, while the anti-MUC-1 antibody titer decreased [210]. The remissions were longer in treated patients and there was a tendency to a decreased risk of relapse [211],... 

Holmberg et al. Bone Marrow transplant, 2000 Theratope sTn-KLH Breast, ovarian CTL... 

A component of Theratope vaccine in phase III clinical trials for use against metastatic breast cancer. Biomira Inc., Edmonton, Canada. 

Clinical Outcome of Breast and Ovarian Cancer Patients Treated after High-Dose Chemotherapy and Autologous Stem Cell Rescue with Theratope (STn-KLH) Cancer Vaccine Theratope (STn-KLH) Cancer Vaccine following Autologous Transplant... 

Between September 1995 and November 2000, 70 patients were vaccinated after autologous peripheral blood stem cell transplantation (ASCT ) with one of two formulations of Theratope (Biomira, Edmonton, Alberta, Canada) coupled with Detox B SE (Detox B) (Corixa, Hamilton, MT). The difference between the two formulations was that the later one has an increased ratio of STn conjugated to KLH compared to the first formulation. The vaccination schedule for the two different formulations was previously published as well as medical treatment history of ASCT patients 18). 

All patients were monitored for toxicity and grading per WHO toxicity criteria. Overall, the vaccine was well tolerated and toxicity has been previously published 18, 19). Most common toxicities seen were local reaction at site of injection including mainly ertheyma and induration and flu like symptoms. The median time to being vaccinated after ASCT with first formulation of Theratope tested was 127.5 days the median time for the second formulation of Theratope was 103 days. 

Blood was collected from patients and clarified. Sera were stored at -80 °C. IgM and IgG titers to OSM or STn were evaluated in serum samples. These antigens were used as the target in solid phase enzyme-linked immunoabsorbant assays before and after treatment with Theratope as previously described 17). 

Event free survival (EPS) and overall survival (OS) of all patients is described by treatment group and relapse risk (Figures 1 and 2, respectively). For these analyses, patients vaccinated with either of the two different formulations of Theratope have been combined. For the whole cohort, there was no statistically significant difference in EFS between control and vaccinated patients after adjusting for risk group. 

Since breast cancer patients were the largest group of patients treated with the two different formulations of Theratope vaccine, we. focused again on evaluating the outcome after vaccination as a function of in vitro immunological responses. Fifty-three patients were available for this analysis. 

As outlined in Table IV, in a multivariable analysis, patients with intermediate and high risk for relapse had greatly increased rates of death compared to lower risk patients. Recipients of the second formulation of Theratope vaccine had a lower risk of death than recipients of the first formulation of vaccine. Higher IgG titers of antibody to OSM was associated with lower rates of death. Proliferative index against STn and OVACAR killing with IL2 or without IL2 stimulation were not stastically significantly different. 

Sandmaier B. M. Oparin D. V. Holmbetg L. A. et al. Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue and immunization with Theratope STn -KLH cancer vaccine. J Immunotherapy 1999, 22, 54-66. 

Holmberg L. A. Oparin D. V. Gooey T. Sandmaier B. The role of cancer vaccines following autologous stem cell rescue in breast and ovarian cancer patients experience with the STn-KLH vaccine (Theratope). Clinical Breast Cancer (Supple) 2003, SI44-150. 

Theratope is a cancer vaccine that consists of modified tumor glycopeptide antigens for patients with advanced breast cancer. The antigen is attached to Keyhole Limpet Hemocy-anin (KLH) protein to increase the immune response to the vaccine. The vaccine uses a carbohydrate antigen known as STn, part of a larger antigen, mucin-1, found on breast cancer cells. Theratope is in phase III human trial, which has as an endpoint of increased survival. 

Theratope (Sialyl Tn Ag conjugate vaccine) Metastatic colorectal, breast cancer Biomira Phase III... 

Anticancer Theratope Therapeutic vaccine for metastatic brest cancer Biomira Inc. Established... 

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