Cancer Vaccine Potency: Is There a Dose/Response Relationship for Patient-Specific Vaccines and Clinical Outcomes?

Abstract

Determination of potency is a challenging problem for patient-specific products derived from autologous cells. For several years, we have been investigating the safety and therapeutic potential of patient- specific vaccines derived from short-term autologous cell lines. We investigated whether clinical potency of these vaccines could be determined by retrospective correlation between the numbers of cells injected (quantity of tumor antigens) and clinical outcome. The averages and standard deviations of irradiated tumor cells were determined for those patients who received the first 3 weekly injections, and for the subset that had a recording of results from tumor delayed-type hypersensitivity testing (DTH). Correlations were made between the numbers of cells injected and DTH conversion and survival. One hundred fifty-six patients received the vaccine product, 136 of whom received the first 3 weekly vaccinations. The most common reason for not receiving 3 injections or having a repeat tumor DTH test was rapidly progressive disease. Ninety-nine patients had cell count data for all 3 injections; 73 had a tumor DTH test at baseline and at week 4. The average number of cells injected over 3 weeks, in millions per patient, by quartile were: 6.0 +/- 1.8, 10.2 +/- 1.4, 15.1 +/- 1.4, and 31.2 +/- 9.8, with respective median survivals of 24.7, 25.5, 24.0, and 21.0 months, with the respective number of DTH conversions being 4, 8, 4, and 6. There were no statistical differences in survival or in the number of patients who had a positive tumor DTH test at week 4. We were unable to define potency--based on a relationship between the number of tumor cells injected as part of vaccination and survival or the reactivity to pure autologous tumor--in a tumor DTH test, over the range of 2-30 million injected cells over 3 weeks.