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CD19/CD22 Dual Target Chimeric Antigen Receptors to Treat Human B-cell Malignancies

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 commercialist the bicistronic CAR construct targeting CD19 and CD22 for immunotherapy.
NIH Reference Number
E-017-2017
Product Type
Keywords
  • Acute Lymphoblastic Leukemia, ALL, Acute Lymphocytic Leukemia, B-cell Lymphoma, Chimeric Antigen Receptor, CAR, CD19, CD22, Immunotherapy, Qin
Collaboration Opportunity
This invention is available for licensing.
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
  • Adoptive immunotherapy
  • CAR-T cells targeting CD19 and CD22 simultaneously to prolong remission
  • Treatment of B cell malignancies, such as ALL
  • Pediatric, blood-derived cancers
Competitive Advantages
  • The lymphoma market is in need of better second-line and maintenance therapies – representing significant opportunities for development within this treatment sector
  • An established, de-risked regulatory path as other bispecifics have reached clinical trials
  • 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 CAR eradicated ALL in a 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)

Haiying Qin MS (NCI), Terry J. Fry MD (NCI)

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
Therapeutic Area
Updated
Thursday, July 25, 2019