Immuno-oncology approaches may transform the way in which numerous cancers are treated

TESARO'S IMMUNO-ONCOLOGY PLATFORM

Antibodies to immune checkpoint receptors have recently demonstrated promise in the treatment of certain solid tumors, including metastatic melanoma, renal cell carcinoma and non-small cell lung cancer. Although the normal function of immune checkpoint receptors is to maintain immune homeostasis, they can be co-opted by certain tumors to evade immune surveillance. PD-1, TIM-3 and LAG-3 are each checkpoint regulators that modulate the function of the immune system via different mechanisms, and may limit the ability of the immune system to respond effectively to tumors. By blocking the interaction of PD-1, TIM-3 and LAG-3 with their respective ligands, antibodies to these targets aim to restore immune anti-cancer function in patients across a variety of tumor types.

PD-1, or programmed death-1, is a key immune checkpoint molecule that can limit T-cell-mediated immune responses. The presence of the PD-1 ligand, PD-L1 has been identified on many tumor types, and expression of PD-L1 has been linked to poor clinical outcomes in a variety of cancers. Anti-PD-1 antibodies have demonstrated in vivo efficacy in tumor models and have shown promising results in several clinical studies.

TIM-3, or T-cell immunoglobulin and mucin domain-3, functions as a pattern recognition receptor that dampens the anti-tumor immune response. Anti-TIM-3 antibodies have shown preclinical anti-tumor activity and may enhance anti-tumor immunity in combination with an anti-PD-1 agent or other immune modulating molecules.

LAG-3, or lymphocyte activation gene-3, is a negative regulator of T-cell activity. Preclinical studies have demonstrated anti-tumor activity by blocking LAG-3 and PD-1 in tumor models, and LAG-3 IgG fusion protein has demonstrated promising results in clinical trials for various solid tumors.