NCI Conference Highlights Promising Advances in Immunotherapy
EASTMAN, PEGGY
Oncology Times:
25 October 2008 - Volume 30 - Issue 20 - p 32-35
Still challenging researchers and slowing progress in the field of cancer immunology and immunotherapy are the inherent complexities of immunity, said other speakers at the meeting.
Regulation of T-cell responses is a lot more complex than we had initially thought, noted James P. Allison, PhD, Director of the Ludwig Center of Cancer Immunotherapy and Chairman of the Immunology Program at Memorial Sloan-Kettering Cancer Center.
Dr. Allison said that one reason there have not been more successful clinical strategies to mobilize the immune system to attack cancer cells is that until recently not enough attention has been paid to the multiple inhibitory mechanisms that serve to shape the immune response and minimize harm to normal tissues.
These mechanisms, he said, are a collective obstacle that can frustrate generation of effective anti-tumor responses.
His research has shown that the prototype of these inhibitory pathways is CTLA4, which limits T-cell proliferation. We have shown that blockade of CTLA4 can greatly enhance anti-tumor responses in a number of experimental tumors in mice, he said, noting that the CTLA4 blocker ipilimumab is now being developed by Medarex, Inc., and Bristol-Myers Squibb.
The results of clinical trials in more than 3,500 patients [for ipilimumab] have demonstrated objective, durable responses in a subset of melanoma, renal, ovarian, and prostate cancer patients. Thus for the first time we have objective responders, which he called exciting.
James C. Yang, MD, Senior Investigator in NCI's Surgery Branch, said that one immunotherapy combination of special clinical interest is ipilimumab plus interleukin-2 (IL-2). Dr. Yang, who chaired a symposium session, noted that in a Phase I/II study of 36 melanoma patients who received dose-escalating ipilimumab with a high-dose bolus of IL-2, the overall response rate was 22%. Long-term follow-up shows that six of the eight responders achieved ongoing complete responses with durations all exceeding four years.
Anti-CTLA4 antibodies have also been tried with other cancers, said Dr. Yang. He added that to extend the role of anti-CTLA4 therapy to a broader array of cancers, it will likely be necessary to combine it with other immunological manipulations, a combination approach which will hopefully boost the host immune response to cancer.
Take Care,
Jimmy B
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