Novel Antibody Conjugate to Treat Pancreatic Cancer
Background
Pancreatic cancer (PC) represents 7% of all cancer mortalities and has a strikingly poor prognosis with PC patients having a 5-year survival rate of less than 8% despite recently intensified studies of immunotherapy and nanomedicine therapy. The immunosuppressive microenvironment of pancreatic cancer tumors presents several challenges to effective treatment. For example, the tumor microenvironment of pancreatic cancer tumors is often characterized by desmoplastic stroma and poor vascularization, which create physical barriers that prevent T-cells or drugs from efficiently infiltrating the tumors. Further, predicting therapeutic sensitivity among patient populations is challenging given the high genetic heterogeneity of pancreatic cancer. There is a need to develop novel targeted therapeutics that can better infiltrate PC tumors while maintaining potent tumor-specific efficacy.
Antibody-drug conjugates (ADCs) are a rapidly growing class of immunotherapeutics that have shown promising clinical efficacy against several types of cancers including aggressive solid tumors like breast cancer, which respond poorly to T-cell immunotherapy. Unlike conventional chemotherapeutics, ADCs utilize chemical linkers to conjugate cytotoxic drugs to tumor-homing antibodies, which are capable of selectively homing tumors while sparing normal tissues via recognizing tumor surface antigens, subsequently internalizing and delivering cytotoxic drugs into targeted tumor cells. However, a major hurdle in developing PC-targeted ADCs is identifying suitable immunotherapeutic targets that effectively distinguish between PC and normal tissues.
Technology Overview
The inventor has developed antibody-drug conjugates (ADCs) as well as a method of treating pancreatic cancer using the ADCs. The inventor has identified and applied intercellular adhesion molecule-1 (ICAM1) as a promising immunotherapeutic target for PC based on an unbiased and quantitative cell-surface target discovery pipeline. The inventor showed that the use of ICAM1 allowed for preferential targeting of pancreatic cancer cells over non-cancerous cells when tested in vivo and further developed a rationally-designed ICAM1 antibody-drug conjugate (ADC) with optimized chemical linker and cytotoxic payload, which induced potent and durable tumor regression in an orthotropic PC model.
Benefits
- Ultra-small size leads to superior tumor tissue penetration compared to other existing therapies
- More effective accumulation in the tumor site and less toxicity to normal tissues
Applications
- Precision medicine approach for pancreatic cancer
- Development of ICAM1-targeting immunotherapeutic
Publications:
Jing Huang, et. al., A Rationally Designed ICAM1 Antibody Drug Conjugate for Pancreatic Cancer, Advanced Science, Dec, 2020
