As I have discussed, immunological therapy will be a significant cancer treatment option in the future, but how will it actually develop and what will it look like?
Provenge (sipuleucel-T), for the treatment of men with advanced prostate cancer, was the first FDA approved autologous immunologic vaccine therapy for any type of cancer. However, Provenge is very expensive ($93,000 US) for the required three rounds of treatment and its manufacturing and administration is rather cumbersome. But, the bottom-line is that it does extend life, the gold standard we all seek.
Immunotherapy is different than chemotherapy. Chemotherapy is designed to attack quickly growing cells which include both the target cancer cells as well as other fast growing healthy cells like your hair and nails. Immunotherapy stimulates a patient’s immune system to attack tumors and ultimately prolong survival.
Provenge works by using the man’s own immune cells (autologous) to stimulate the immune system to attack tumors ultimately prolonging a man’s survival. However, every dose of Provenge is personalized and made to order for each individual patient, a costly and inefficient process.
I am pleased that autologous immunologic therapy will progress and become both less expensive and easier to administer as our experience grows. However, despite the logistical and manufacturing challenges of personalized immune cell therapy, Provenge is relatively safe and can elicit a sufficient immune response against tumors to improve survival.
Prior to the approval of Provenge in 2010 to treat advanced prostate cancer; many researchers questioned whether an autologous cancer immunotherapy was commercially viable. Dendreon (the makers of Provenge) has shown that Provenge can be both scalable and profitable, but the logistics remain a limiting factor in its use and availability.
The good news is that the newer autologous cellular cancer immunotherapies that are under development may also be more effective and will probably be able to overcome Provenge’s logistical shortcomings. Immunocellular Therapeutics (IMUC) and Northwest Biotherapeutics are developing investigational immune therapies that also utilize a patients’ dendritic cells. IMUC is currently enrolling patients in a randomized, multi-center, double-blinded, Phase II study for its investigation treatment ICT-107 for patients with glioblastoma multiforme, a very aggressive form brain cancer.
Unlike Provenge which uses one tumor associated antigen, PAP, ICT-107 uses six tumor-associated antigens to target tumor cells as well as cancer stem cells, which are more resistant to radiation and chemotherapy. The results from the Phase I study of ICT-107 improved patient survival by almost two years compared with the historical standard of care.
Coupling this improved survival advantage, the manufacturing data released last week from current phase II manufacturing experience shows that it is possible to produce 60 doses (30 product and 30 placebo) from a single manufacturing run. According to the IMUC company presentations, the cost per shot of vaccine would be under $500 per shot of vaccine with per shot. This compares very favorably with the cost of manufacture for Provenge, which is approximately $15,000 with a retail cost of about $31,000 per infusion.
Lower Cost, Better Logistics – A Look Forward
Like Provenge, patients treated with either ICT-107 or the Northwest Biotherapeutics product DCVax also undergo a leukapheresis procedure to harvest their dendritic cells. However, the dendritic cell manufacturing process they have been able to use has become much more efficient. One leukapheresis procedure with ICT-107 manufacturing process can produce as many as 30 doses.
ICT-107 and DCVax can be stored in a freezer, so patients only need to undergo one leukapheresis procedure instead of three as with Provenge. This change eliminates the need to ship the final product back to patients within 18 hours (as is required for the use of Provenge) creating the need to have multiple manufacturing facilities as Dendreon has been forced to establish. ICT-107 and the DCVax can be administered by intra-dermal injection rather than IV infusion, which is much less invasive and time consuming for patients.
We all benefit from the fact that new therapeutic modalities improve with each new generation. It is just a matter of time when autologous cellular immunotherapies evolve into more commercially optimal products, allowing for better access for many more individuals.
Joel T Nowak, M.A., M.S.W.