Janssen Pharmaceutica Nv

Janssen Pharmaceuticals, Inc.

Jon M Richards

Per A Peterson

Ann M Moriarty

Michael R Jackson

Zeling Cai

Didier J Leturcq

T cell responses are often diminished in humans with a compromised immune system. We have developed a method to isolate, stimulate and expand na&#xef;ve cytotoxic T lymphocyte precursors (CTLp) to antigen-specific effectors, capable of lysing tumor cells in vivo. This ex vivo protocol produces fully functional effectors. Artificial antigen presenting cells (AAPCs;) transfected with human HLA class I and defined accessory molecules, are used to stimulate CD8T cells from both normal donors and cancer patients. The class I molecules expressed to a high density on the surface of thecells are empty, allowing for efficient loading of multiple peptides that results in the generation of polyclonal responses recognizing tumor cells endogenously expressing the specific peptides. The responses generated are robust, antigen-specific and reproducible if the peptide epitope is a defined immunogen. This artificial antigen expression system can be adapted to treat most cancers in a significant majority of the population.

Cell therapy method for the treatment of tumors

In a cancer treatment combining cell therapy with chemotherapy, autologous CD8T cells are obtained from a patient, activated ex vivo by contacting them with xenogenic antigen presenting cells loaded with selected peptide antigen, thereby generating antigen-specific activated cytotoxic T lymphocytes. Such activated CTLs are administered to the patient in conjunction with a lymphodepletion and CTL maintenance regimen comprising a non-myeloblative but lymphdepleting agent, such as cladribine or denileukin diftitox, and interleukin-2 and interferon-&#x3b1;-2b stimulatory cytokines.

Cancer treatment combining lymphodepleting agent with CTLs and cytokines

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Glenview, IL, United States of America

Jon M Richards