Summary of Invention
Most tumor cells function poorly as antigen-presenting cells in part because they do not express co-stimulatory molecules but also because tumor antigens are self antigens, and thus are poorly immunogenic.
See Figures.
Chimeric antigen receptors capable of delivering both primary and co-stimulatory signals to genetically modified T cells are generated and used to treat tumors and B cell malignancies (Figure 1).
Genetically modified T cells targeted to (i.) PSMA, an antigen present in prostate cancer; (ii.) GD2, a ganglioside overexpressed on the surface of neuroblastoma, small cell lung carcinoma, melanoma, and other human tumors; or (iii.) the CD19 antigen overexpressed in B cell malignancies are expanded (Figure 2). Those expanded T cells retain a functional phenotype, including in vivo cytolytic activity and the ability to traffic to tumor sites without prematurely succumbing to apoptosis.
Most recent results using cells targeted to the CD19 antigen show that in tumor-bearing SCID-Beige mice, injected T cells persist and eradicate disseminated intramedullary tumors as evidenced by both long-term survival and positron emission tomography (see Figure 3).
Advantages
For treatment of B cell malignancies, prostate cancer, and neuroblastoma; elimination of any tumor cells presenting a specific tumor antigen.
Areas of Application
Adoptive cell therapy.
Stage of Development
Proof of concept obtained in mice.
References
Lead Inventor:
Dr. Michel Sadelain
Patent Information
- US prosecution ongoing (SK 766).
- PCT application published as WO0014257. Patent prosecution ongoing in US and in several major countries (SK 867).
- US prosecution ongoing (SK1036).
Contact Information
Viviane Martin, PhD
Tel: 212-639-6181; Fax: 212-717-3439
E-mail: martinv@mskcc.org
