Phase I trial of a B7-1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma
SJ Antonia, J Seigne, J Diaz, C Muro-Cacho… - The Journal of …, 2002 - auajournals.org
SJ Antonia, J Seigne, J Diaz, C Muro-Cacho, M Extermann, MJ Farmelo, M Friberg…
The Journal of urology, 2002•auajournals.orgPurpose: A reason that the immune system may fail to reject tumors is that T cells encounter
tumor antigen derived peptides on the surface of tumor cells in a tolerizing rather than
activating context since tumor cells do not express T cell co-stimulatory molecules such as
B7-1 (CD80). In preclinical models over expression of B7-1 on the surface of tumor cells has
been shown to activate T cells which kill tumor cells. We conducted a phase I clinical trial
testing this approach in patients with metastatic renal cell carcinoma. Materials and …
tumor antigen derived peptides on the surface of tumor cells in a tolerizing rather than
activating context since tumor cells do not express T cell co-stimulatory molecules such as
B7-1 (CD80). In preclinical models over expression of B7-1 on the surface of tumor cells has
been shown to activate T cells which kill tumor cells. We conducted a phase I clinical trial
testing this approach in patients with metastatic renal cell carcinoma. Materials and …
Purpose
A reason that the immune system may fail to reject tumors is that T cells encounter tumor antigen derived peptides on the surface of tumor cells in a tolerizing rather than activating context since tumor cells do not express T cell co-stimulatory molecules such as B7-1 (CD80). In preclinical models over expression of B7-1 on the surface of tumor cells has been shown to activate T cells which kill tumor cells. We conducted a phase I clinical trial testing this approach in patients with metastatic renal cell carcinoma.
Materials and Methods
Resected tumors from 15 patients were disaggregated and adapted to tissue culture, transduced with the B7-1 gene and injected subcutaneously as a vaccine. The dose of the vaccine was escalated in 3 separate cohorts of patients, and systemic interleukin-2 (IL-2) was administered as an adjuvant designed to enhance the proliferation of the vaccine activated T cells.
Results
Of the 15 patients 9 had measurable disease, 2 had a partial response and 2 had stable disease. Perivascular T cell infiltrates at autologous tumor delayed type hypersensitivity skin test sites developed in 3 of the 4 patients with stable disease or partial response. Although the patients experienced the usual and expected toxicity from the IL-2, there was no significant toxicity observed with the vaccine.
Conclusions
The B7-1 gene modified autologous tumor cell vaccine is safe and can be combined with systemic IL-2 with acceptable toxicity. Immunological and clinical responses were observed in some of the patients. A phase II trial is reasonable to determine the efficacy of this approach.
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