On September 06, 2017 (GLOBE NEWSWIRE) — Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported in a poster session the presentation of new research from investigators at the company on the application of Endocyte’s SMDC technology in a chimeric antigen receptor (CAR) therapy setting (Poster #5 Targeting a universal CAR-T cell for effective anti-tumor activity and enhanced control using bi-specific small molecule adaptors) at the 2017 CAR-TCR Summit, in Boston, MA (Press release, Endocyte, SEP 6, 2017, View Source [SID1234520392]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The clinical success and recent regulatory approval of the first CAR T-cell therapy has shown the efficacy of CAR T-cell technologies in hematological malignancies and the potential promise of the treatment in solid tumors as well. However, these therapies remain limited in their potential use due to hard to manage, clinically significant toxicities, specifically cytokine release syndrome (CRS). The data presented demonstrate the potential of Endocyte’s targeted bi-specific SMDC adaptors to improve upon the safety of current CAR T-cell approaches," said Mike Sherman, president and CEO at Endocyte. "This is particularly relevant as we advance our CAR-T program in solid tumors, including the previously announced clinical evaluation of our program in osteosarcoma being led by Dr. Michael Jensen of Seattle Children’s Research Institute."
Endocyte’s clinical plan includes genetically engineering a patient’s autologous T-Cells to express receptors that recognize fluorescein. Once these T-Cells are infused back into the patient, Endocyte researchers will then introduce its bi-specific adaptor molecules, which are constructed with both a fluorescein molecule and a tumor-homing molecule (e.g. folate) to precisely tether a universal CAR T-cell to a cancer cell. This approach causes local CAR T-cell activation within the tumor, followed by cancer cell death. The current presentation discloses an advancement of Endocyte’s method showing the application of specific blocking agents to control undesirable toxicity that often accompanies CAR-T therapy, including CRS, while simultaneously offering the potential to target multiple proteins on the diseased cell (folate, PSMA, NK1R, et al). Strategies are revealed for regulating cytokine storms, including: simple interruption or less frequent administration of the bi-specific adaptor, and injection of untethered folate or sodium fluorescein to rapidly (within hours) displace or block the bi-specific adaptor from bridging the cancer and CAR T-cells. Since the circulation half-life of most bi-specific adaptors is approximately 30 minutes, unwanted toxicity from CAR T-cell induced cytokine storms can be either pre-emptively prevented or rapidly suppressed following their emergence.
"Our pre-clinical data clearly show that a targeted bi-specific adaptor approach can effectively be used to more safely regulate CAR-T therapy for solid tumors," said Chris Leamon, Ph.D., vice president of research at Endocyte. "Knowing the unwanted toxicity can be controlled by administering clinically-approved agents is potentially a powerful advantage."
About Endocyte’s SMDC Bi-Specific Adaptors
Endocyte’s SMDC bi-specific adaptors represent a novel approach that makes possible the engineering of a single universal CAR T-cell, designed to bind with high affinity to FITC. This universal CAR T-cell can be specifically directed to cancer cells through the administration of a tumor targeted FITC-containing SMDC, known as a bi-specific adaptor that acts to bridge the universal CAR T-cell with the cancer cells to cause localized T-cell activation. This approach has been shown pre-clinically to address three key CAR T-cell issues by: (i) avoiding hyper-activation of CAR T-cells leading to a cytokine storm, (ii) enabling termination of CAR T-cell activity upon eradication of the tumor, and (iii) potentially enabling elimination of all cancer cells in heterogeneous solid tumors. In March 2017, Endocyte entered into a research collaboration with Seattle Children’s Research Institute and Dr. Michael Jensen for the development of Endocyte’s SMDC platform in CAR T-cell immunotherapy setting through the use of Endocyte’s proprietary SMDC bi-specific adaptor molecules.