RESEARCH & DEVELOPMENT

Individualised prostate cancer vaccine immunogenic

A granulocyte-macrophage colony-stimulating factor (GM-CSF) genetically-engineered prostate cancer vaccine, using cancer cells removed from an individual's own prostate tumour, successfully elicits systemic immune responses against prostate cancer antigens, report US-based researchers.

In this phase I trial, 8 immunocompetent men with advanced prostate cancer following radical prostat­ectomy received ~ 6 intradermal injections of cultured, lethally irradiated, autologous prostate cancer cells genetically engineered to express human GM-CSF, every 3 weeks. Prostate cancer cells were harvested from individual patients' radical prostatectomy resection specimens.

Following vaccination, 7/8 men demonstrated positive delayed-type hypersensitivity (DTH) tests to challenge with irradiated, untransduced autologous prostate cells. In addition, histopathological and immunohistochemical analysis of reactive DTH site biopsies taken after vaccination revealed extensive eosinophil infiltrates and a subendothelial eosino­philic vasculitis, as well as T cells.

After vaccination, immunoblot analyses revealed increased titres of antibodies recognising prostate tumour antigens in sera from 3/8 men.

Adverse events consisted of mild, low-grade fevers, chills and malaise, as well as acute vaccine site effects.

The researchers say that their results' suggest that systemic immune responses to human peA [prostate cancer] can be generated against a tumor type that has been conventionally viewed as being nonimmuno­genic, and refractory to immunotherapy' . Simons IW. Mikhak B. Chang J-F. DeMarzo AM. Carducci MAo et aI. Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate IUmOr cells enginccrcd to secrete granulocyte­macrophage colony-stmuJating factor using ex vivo gene transfer. Cancer Rcscan:h 59: 5l6C}.5168. 15 Oct 1999 l00I01126

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Inpharma-'3 Noy 1999 No. 1213