Ira Pastan, M.D.

Mesothelin as a Target for Cancer Therapy by CAR-T cells and Bispecific Antibodies

1.2 million Americans develop cancer each year and about 500,000 die from the disease. To improve the therapy of cancer new approaches and drugs with unique mechanisms of action are needed. Mesothelin is a lineage restricted cell surface protein that is highly expressed by many cancers, and onlya few non-essential tissues. The specificity of mesothelin expression makes it a popular target for antibody-based therapies, but shed mesothelin has been found to be a major barrier to these therapies. To overcome this problem we developed Mab 15B6 that binds to a juxta-membrane region of mesothelin and does not bind to shed mesothelin. Mab 15B6 was used to make CAR T cells and bispecific antibodies (T cell engagers) that have high anti-tumor activity in mice. A CAR-T is being prepared for evaluation in humans.

Dr. Ira Pastan was educated at the Boston Public Latin School, Tufts College, and Tufts Medical School. He did his residency at the Yale School of Medicine (1957-1959) and came to NIH in 1959. In 1970, he founded the Laboratory of Molecular Biology in the NCI.

Major honors

Van Meter Prize, 1971

G. Burroughs Mider Lectureship, National Institutes of Health, 1973

Membership, National Academy of Sciences, 1982

American Academy of Arts and Sciences, 1997

Fellow, American Academy of Microbiology, 1997

Fellow, American Association for the Advancement of Science, 1997

International Feltrinelli Prize for Medicine, 2009

Nathan Davis Award of the AMA for Government Service, 2010

Membership, Institute of Medicine of the National Academies, 2010

AACR Team Science Award, 2014

Humbert Humphrey Award, DHHS, 2019

Samuel J. Heyman Service to America Medals, 2020