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4-1BB agonist monoclonal antibodies: PF-05082566 in combination with Rituximab in patients with relapsed or refractory CD20+ non-Hodgkin’s lymphoma


PF-05082566 ( PF-2566 ) is an investigational immunotherapy and fully humanized monoclonal antibody administered intravenously that stimulates signaling through 4-1BB ( CD-137 ), a protein expressed in many immune cells.

The 4-1BB ( CD-137 ) protein receptor is found on T cells such as CD8+ T cells, natural killer cells and CD4+ T cells.
Based on pre-clinical data, when PF-2566 binds to 4-1BB, it stimulates and increases the number of immune cells. This may provide enhanced anti-tumor immune function.
This is different from checkpoint inhibitors ( i.e. PD-1, PD-L1 ), which act on another immune signaling pathway and are believed to work by inhibiting suppression of T cells.

Preclinical studies suggest that combining PF-2566 with a checkpoint inhibitor, such as anti-PD-L1, or other immunotherapies may be able to amplify the immune response.

Further understanding the biology of how the immune system attacks tumors and ways by which tumors evade the immune system may lead to a variety of promising combinations in the future.

Pfizer is exploring the potential of PF-2566 in a clinical development program to determine: (a) the maximum tolerated dose (b) efficacy and (c) therapeutic potential in combination with other therapies.

Data from a Phase 1 study that evaluated PF-2566 ( 4-1BB ) in combination with Rituximab in patients with relapsed or refractory CD20+ non-Hodgkin’s lymphoma ( NHL ) presented at the 2015 ASCO Annual Meeting showed that 4-1BB demonstrated anti-tumor activity.
No dose-limiting toxicities were observed and no patients discontinued treatment due to treatment-related adverse effects.
These results characterize the potential efficacy for this investigational immunotherapy when used in combination with a drug such as Rituximab that has a different MOA. ( Xagena )

Source: Pfizer, 2015

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