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Dual Specific Anti-CD22 Anti-CD19 Bicistronic Chimeric Antigen Receptors (CARs)

Summary
Inventors at the National Cancer Institute (NCI) have developed chimeric antigen receptors (CARs) that target two B cell surface antigens, CD19 and CD22, improving treatment of B-cell malignancies, such as acute lymphoblastic leukemia (ALL). NCI is actively seeking parties interested in licensing this invention to commercialize the bicistronic CAR construct targeting CD19 and CD22 for immunotherapy.
NIH Reference Number
E-017-2017
Product Type
Keywords
  • Dual-Specific Chimeric Antigen Receptors, CAR, Bicistronic, CD19, CD22, Oncology, Acute Lymphoblastic Leukemia, ALL, Diffuse Large B-Cell Lymphoma, DLBCL, Pediatric Leukemia, Pediatric Lymphoma, Fry
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

Treatment of B-cell acute lymphoblastic leukemia (ALL) and lymphoma using chimeric antigen receptors (CARs) targeting B-cell surface protein CD19 has demonstrated impressive clinical results in children and young adults. Despite the promising results from CD19 CAR therapy, up to 40% of patients, who initially achieve remission, eventually relapse. Relapse or non-response to CD19-directed CAR therapy may be due to low or diminished CD19 expression. Such patients would be predicted to benefit from CAR therapies targeting other B-cell surface proteins, such as CD22.

Scientists at the National Cancer Institute’s (NCI) Pediatric Oncology Branch have developed a novel, bicistronic CAR construct targeting both CD19 and CD22 simultaneously. Specifically, the construct encodes both CD19 and CD22 on the same vector, ensuring comparable levels of targeting activity against both proteins. CAR-T cells produced with this construct eradicated relapsed ALL models, including one derived from a patient that displayed relapse after CD19-directed therapy. To date, this bicistronic approach exhibits the best results in CAR-T models of pre-B cell ALL.

NCI is actively seeking parties interested in licensing this invention to commercialize the bicistronic CAR construct targeting CD19 and CD22 for immunotherapy.

Potential Commercial Applications
  • Treatment of acute lymphoblastic leukemia (ALL), the most common form of cancer for children
  • Treatment of additional b cell malignancies including Diffuse Large B-Cell Lymphoma (DLBCL)
  • Adoptive immunotherapy
Competitive Advantages
  • The leukemia/lymphoma market is in need of better second-line and maintenance therapies – representing significant opportunities for development within this treatment sector
  • Overcomes durability of response – currently a major limitation – resulting from resistance mechanisms involving the downregulation of target antigen CD19 from tumor cell surfaces
  • First demonstration of an active dual CAR targeting two naturally expressed antigens on ALL
  • Bicistronic construct ensures that CARs will target both CD19 and CD22 efficiently
  • CD19/CD22 bicistronic CAR demonstrated enhanced efficacy in an ALL xenograft model derived from a patient with relapse following CD19-directed therapy
  • Successful ablation of ALL in various cell line and patient-derived xenograft models
Inventor(s)

Terry J. Fry MD

Development Stage
Publications

Qin H, et al. Novel CD19/CD22 Bicistronic Chimeric Antigen Receptors Outperform Single or Bivalent CARs in Eradicating CD19+CD22+, CD19-, and CD22- Pre-B Leukemia.  [Blood 2017 130:810]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/506,268 , Filed 15 May 2017
  • PCT: PCT Application Number PCT/US2018/032809 , Filed 15 May 2018
  • U.S. Patent Filed: U.S. Patent Application Number 16/613,187 , Filed 13 Nov 2019
Therapeutic Area
Updated
Monday, March 1, 2021