Evaluation of circulating tumor cell gene expression profiles before and following combination immunotherapy for advanced prostate cancer

Autor: Bernard A. Fox, Sachin Puri, Walter J. Urba, Christopher Dubay, Bharat H. Joshi, Brendan D. Curti, Christopher Paustian, Keith S. Bahjat, Jing Han, Janet C. Siebert, Daniel Healy
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Journal for Immunotherapy of Cancer
ISSN: 2051-1426
Popis: The Phase I/II clinical trial randomized patients to GVAX immunotherapy (two prostate cancer cell lines that secrete GM-CSF, Cell Genesys Inc.) alone or in combination with non-myeloablative chemotherapy and adoptive transfer of PBMC. Pre and week 11 aphereses were obtained to elutriate monocytes and cryopreserve PBMC for immune monitoring. We used ProtoArrays (8,217 proteins spotted arrays, Invitrogen) to evaluate the week 11 post treatment antibody responses of 11 patients who completed this IRB-approved DAMD-funded clinical trial for men with androgen-independent prostate cancer. Analysis of pre and week 11 sera identified increased antibody responses to a number of proteins and the patients with an increase in PSA-doubling time (PSA-DT) exhibited a strong response to a significantly (p 1.5 fold compared to a normal prostate tissue control. Current efforts are aimed at evaluating whether targets of the antibody response were contained in the oligonucleotide array and whether proteins for genes that decreased in intensity were contained on the protein array. The methods we describe may help assess whether a given treatment is inducing strong immune response and whether this immune response is sculpting the repertoire of antigens expressed by the tumor. Such tests are currently not available and development of such a test may aid the development and refinement of the novel combination immunotherapy strategies.
Databáze: OpenAIRE
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