Pocket Drug Guide

The Memorial Sloan-Kettering Cancer Center in New York is developing a series of peptides from the breakpoint of the BCR-ABL gene as vaccines for the potential treatment of chronic myelogenous leukemia. The peptides are in Phase II trials.

The peptides are derived from the amino acid sequences crossing the b3a2 breakpoint of the BCR-ABL-generated 210 kDa oncogene product. The peptides have been shown to bind major histocompatibility complex (MHC) class I molecules, thereby eliciting CTL responses.

In a Phase II trial, 14 patients with chronic myelogenous leukemia in the chronic phase with any HLA type and a b3a2 BCR-ABL breakpoint were vaccinated subcutaneously five times over a ten-week period using a preparation of six peptides mixed with the adjuvant Quillaja saponaria (Antigenics’ QS-21). All patients developed delayed-type hypersensitivity (DTH) and/or CD4 proliferative responses after beginning vaccinations, and 11 of 14 patients showed IFN-y release by CD4 enzyme-linked immunospot (ELISPOT) at one or more time points. Four patients in hematologic remission had a decrease in Ph chromosome percentage; three patients in molecular relapse after allo-Stem-cell transplantation became transiently PCR-negative after vaccination.

In another Phase II trial, a total of 16 evaluable chronic-phase chronic myelogenous leukemia patients who had achieved major cytogenetic response or cytogenetic response that had been stable for at least six months during conventional treatment with interferon-a or imatinib, and who had a b3a2 BCR-ABL breakpoint, were vaccinated subcutaneously six times over a 12-week period (every two weeks) using a preparation of five peptides mixed with QS-21 and GM-CSF. Patients who had an immune response received two booster vaccinations at four- and eight-month intervals after the date of the last vaccination. No significant toxic effects were observed. Thirteen patients developed CD4 proliferative responses, and 9 out of 16 developed DTH. Of 10 patients who had been previously treated with imatinib, a molecular response was noted in 6 (including three cases with undetectable levels of BCR-ABL). In 6 patients previously treated with interferon-a, 2 showed a response (one cytogenetic and one molecular).

Comments are closed.