Blood
VAX100 : A Vaccine for Chronic Myeloid Leukemia (CML)
By Akanksha, Pharmacology Correspondent
Mar 2, 2005, 14:34

Breakthrough Therapeutics, a privately owned biotechnology company, today announced the publication of positive data with a vaccine for chronic myeloid leukemia (CML) known as VAX100, in the Journal Lancet.

VAX100 is a BCR-ABL peptide vaccine designed to reduce persistent disease in patients with CML whom have had stable disease during conventional therapy. Breakthrough Therapeutics has licensed the peptides associated with the BCR-ABL breakpoint (including those used in VAX100) from Memorial Sloan Kettering Cancer Center.

Of the six patients whom had previously been treated with interferon alpha for a minimum of 17 months stable residual disease 5 (83%) had improved cytogenetic response with 2 patients achieving CCR. All patients received six injections of VAX100 vaccine on a biweekly schedule. During vaccinations, patients continued conventional treatment. Assessment of cytogenetic response and confirmation of molecular remission took place every 3 months.

Breakthrough is currently optimizing the current formulation of the components of VAX100 to enhance its antigenicity. It will be the optimized formulation, to be named CMLVAX500, which will be taken into additional Phase II trials.

"The best surrogate for long term survival in patients with CML is to achieve a complete molecular remission. While drugs like Gleevec have revolutionized the treatment of CML, not all patients achieve a complete cytogenetic remission and most maintain detectable disease at the molecular level," commented Rosemary Mazanet, M.D., Ph.D., Breakthrough Therapeutics' Co-founder and Chief Executive Officer. "It is our hope that the addition of a BCR-ABL specific vaccine to conventional treatment may further increase the proportion of patients who achieve a reduction of residual disease. The positive results from VAX100 suggest that the enhanced antigenic BCR-ABL peptides may achieve similar results. That would mean a significant step for patients with CML."

David Scheinberg, M.D., Ph.D., Chairman, Molecular Pharmacology & Chemistry, Memorial Sloan-Kettering Cancer Center and the inventor of the BCR-ABL peptide vaccine strategy used by Dr. Monica Bocchia and colleagues commented, "While these data are early we are very encouraged by the results of this study and we look forward to initiating additional clinical trials with our colleagues in the near future."

Sixteen patients with stable residual disease, all of whom received a minimum of either 12 months of imatinib mesylate (Gleevec(R), Novartis) or 24 months of interferon alpha, received a total of 6 vaccinations with VAX100 every other week. Of the 10 patients on imatinib, 9 whom had a median of 10 months of residual disease and 1 patient who started with complete cytogenetic remission (CCR, where cytogenetics are normal on a bone marrow biopsy), all 10 of these patients had improved cytogenetic responses with 50% achieving a CCR. Three of these 5 patients also had undetectable amount of b3a2 transcript (a tumor-specific antigen seen at the fusion point of BCR-ABL).

Chronic myeloid leukemia (CML) is a form of leukemia caused by the abnormal growth of relatively mature white blood (myeloid) cells. CML affects 1 to 2 people in 100,000 and is responsible for 15% to 20% of all adult leukemia. CML is characterized by a specific chromosomal abnormality called the Philadelphia (Ph) chromosome.

The Ph chromosome is the result of a translocation between two genes, which brings together the BCR (breakpoint cluster region) gene on chromosome 22 and the proto-oncogene ABL (Ableson leukemia virus) on chromosome 9. The resulting hybrid gene BCR-ABL activated signaling pathways that lead to uncontrolled cell growth.

All rights reserved by www.rxpgnews.com