Immune Response and Immunotherapy: Live Attenuated Listeria monocytogenes (Lm)-LLO Immunotherapy for the Treatment of Prostate Cancer

Anu      Wallecha; Robert      Petit; Chris      French; John      Rothman

Abstract

There is an unmet need for new approaches to treat prostate cancer beyond hormonal deprivation and chemotherapy. Using immunotherapy to focus immune responses on prostate cancer antigens appears to be a valid therapeutic approach. Several immunotherapeutic agents are being developed employing a variety of approaches. In recent years, Listeria monocytogenes (Lm)-LLO immunotherapy has been well tolerated in early clinical studies and is currently being evaluated in the clinic for HPV-associated dysplasia and malignancies such as recurrent/refractory cervical cancer, cervical intraepithelial neoplasia (CIN) 2/3, and head and neck cancer. Lm is a strong stimulator of both innate and cellular immune responses due to its unique life-cycle. Attenuated Listeria-based Lm-LLO immunotherapy secreting human prostate specific antigen (PSA) (ADXS31-142) has been shown to cause the therapeutic regression of PSA-expressing tumors in mouse models. The therapeutic effect of ADXSD31-142 on tumor regression is associated with the generation of PSAspecific T cells and subsequently, their infiltration in the tumor microenvironment, accompanied by the reduction of regulatory T cells (CD4+CD25+Foxp3+) within the tumors. Further development is underway to advance ADXS31-142 Lm- LLO immunotherapy into the clinic for the treatment of castration resistant prostate cancer.

Keywords: ADXS-PSA, Antigen-adjuvant fusion protein, Immunotherapy, Listeria monocytogenes, Lm-LLO, listeriolysin O, prostate cancer vaccine

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