Targeted cancer therapy is gaining significant importance due to in part with the rapid improvement in understanding of the human immune system. Anti-CTLA41, anti-PD1, and anti-PDL1 are immuno-oncology breakthrough drugs in the cancer treatment. Metastatic cutaneous melanoma has been the disease that has provided overwhelmingly positive early evidence of IO therapy safety and efficacy, but it is becoming clear that this drug class is effective against many other cancers2,3. In 2016, there were &gt;250 ongoing clinical trials involving IO drug and drug candidate combinations3. These IO drug and clinical candidates unblock or directly activate the secondary signals that T cells require to stay fully activated in the tumor microenvironment. Unfortunately, not all cancer patients respond and most patients experience mild to moderate adverse immune events during or following the treatment4,5. Here we show that adding multiple copies of a targeting ligand for lung cancer to murine anti-PD1 enables the conjugate to specifically bind cells and concentrate at syngeneic murine tumors that express the targeted lung cancer-specific receptor. The tumor targeting allows for the use of safer doses of targeting ligand-anti-PD1 conjugate that reduced lung tumor burden and significantly extended survival after a single dose. The proof of concept studies with lung cancer targeting of murine anti-PD1 can be expanded to a fully humanized version and other IO agents can be lung cancer targeted using the same approach. Other cancer-specific targeting ligands may also be used to design tumor-specific IO agents for those respective cancers6,7.

Immuno-oncology (IO) drug conjugate concentrates at cells and tumors and enhances survival

2019 Spring National Meeting

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