Early Results for MDX-CTLA4 are Promising
April 09, 2003
In a paper published this week in Proceedings of The National Academy of Sciences, Hodi, Dranoff et al validated the advancement of Medarex’s (NASDAQ: MEDX) MDX-CTLA4 (MDX-010) into more advanced phase I investigation and efficacy-deriving clinical trials. In this preliminary phase I study, nine previously immunized patients with advanced cancer were infused with MDX-CTLA4. MDX-CTLA4 appeared to increase anti-tumor immunity in certain recipients. Evidence that immunostimulation occurred with acceptable benefit/risk included:
extensive tumor necrosis (cell death) was observed with specific biological correlates in three of three metastatic melanoma patients
reduction or stabilization of CA-125 levels was observed in two of two metastatic ovarian carcinoma patients pretreated with autologous granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cells
antibody-attributable toxicity profile was reassuring.
Difficulties with the therapy include potentially adverse immunologic attack of normal, as opposed to cancerous, skin cells for recipients with melanoma, and certain suboptimal therapeutic responses for these patients.
Since cancer patients’ immune systems rarely impede disease progression on their own, cancer vaccines and augmenting therapies such as this one are being developed to stimulate natural anti-tumor immune responses. This boosting of the patient immune response theoretically can be achieved by vaccinations that enhance specific immune responses. In this case, the nine patients were immunized with several different types of cancer vaccines, including modified irradiated autologous tumor cells and modified dendritic cells.
Medarex’s strategy is to increase the immune response to tumors after vaccination by boosting the anti-tumor immune response with MDX-CTLA4. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a protein that attenuates T cell activation, and is thought to dampen the already weak anti-tumor responses in many patients. Compelling preclinical evidence, primarily from murine cancer models, shows that antibodies blocking CTLA-4 function, alone and in combination with certain cancer vaccines, inhibit the growth of certain tumors.
pcsresearch.com
John McCarthy |
