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Unexpected Association between Induction of Immunity to the Universal Tumor Antigen CYP1B1 and Response to Next Therapy
Purpose: The carcinogen activator cytochrome P450 1B1 (CYP1B1) is expressed on almost all human tumors with rare expression on normal tissues. Anti-CYP1B1–specific T cells kill CYP1B1-expressing tumors, providing the rationale to examine CYP1B1 as a target for immunotherapy. Experimental Design: ZYC...
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Published in: | Clinical cancer research 2005-06, Vol.11 (12), p.4430-4436 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Purpose: The carcinogen activator cytochrome P450 1B1 (CYP1B1) is expressed on almost all human tumors with rare expression on normal
tissues. Anti-CYP1B1–specific T cells kill CYP1B1-expressing tumors, providing the rationale to examine CYP1B1 as a target
for immunotherapy.
Experimental Design: ZYC300, a plasmid DNA of CYP1B1 encapsulated in biodegradable poly- dl -lactide-coglycolide microparticles, was used in a phase I clinical trial to treat 17 patients with advanced stage, progressive
cancer. ZYC300 was administered i.m. at a fixed dose of 400 μg every other week for up to 12 doses.
Results: Thirteen patients received six vaccinations and five received all 12 doses. No significant adverse events were observed.
Six patients developed immunity to CYP1B1, three of whom developed disease stabilization. All but 1 of 11 patients who did
not develop immunity to CYP1B1 progressed and did not respond to salvage therapy. Five patients who developed immunity to
CYP1B1 required salvage therapy for progressive metastatic disease and showed marked response to their next treatment regimen,
most of which lasted longer than 1 year.
Conclusions: The association between immunity to CYP1B1 and response to next salvage therapy was not expected. Because six of the seven
patients who had clinical benefit regardless of the nature of salvage therapy had developed immunity to CYP1B1, it seems highly
unlikely that this occurred by chance alone. Regardless of the mechanism(s) that induced tumor regression, these findings
force us to rethink how the generation of antitumor immunity might be integrated into the treatment of cancer. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-04-2111 |