T Cell Gene Therapy to Eradicate Disseminated Breast Cancers
Abstract
There is no cure for metastatic breast cancer, which kills 40,000 American women (and 500 men) each year: all presently available treatments are palliative. Gene therapy techniques are used to introduce chimeric immunoglobulin-T cell receptors (IgTCR) into autologous patient T cells to create designer T cells that redirect the T cell immune system in a new type of immuno-gene therapy against breast cancer. Designer T cells have been created against the carcinoembryonic antigen (CEA) that is prominently present on many metastatic breast tumors (30-60%). This exceeds the fraction that are Her2/neu overexpressing (20-25%), making CEA an even better immune target for attacking breast cancer. Building on a prior study of CEA designer T cells in breast and colon cancer, 2nd generation designer T cells were created by incorporating into the IgTCR a CD28 co-stimulation cassette that was shown to oppose activation-induced cell death (AICD) of the T cells after tumor contact. This advanced generation modification leads to improved designer T cell survival and improved anti-tumor potency in preclinical models. Although the 2nd generation designer T cells produce interleukin 2 (IL2) growth factor on contact with tumor, interleukin 2 (IL2) supplementation is anticipated still to be required for optimal clinical therapeutic effect. However, the CBER/FDA has mandated a Phase I.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2012
- Accession Number
- ADA567468
Entities
People
- Richard P. Junghans
Organizations
- Roger Williams Medical Center