I-Mab Announces Multiple Presentations at the 2022 American Association for Cancer Research (AACR) Annual Meeting
SHANGHAI and
"We continue to make significant progress in advancing our innovative pipeline to generate the next wave of novel cancer therapeutics for patients around the world," said Dr.
Enoblituzumab is a highly differentiated humanized monoclonal antibody directed against the immune regulator B7-H3, which has been associated with poor prognosis and is widely expressed in multiple cancers. Enoblituzumab mediates the antibody-dependent killing of cancer cells and has demonstrated strong anti-tumor activity in preclinical studies. Currently,
TJ-C64B is the third bispecific antibody with a conditional T cell engager based on 4-1BB-activation platform. It binds simultaneously to Claudin 6 (CLDN6)-expressing cancer cells and the costimulatory molecule 4-1BB. CLDN6 is a tight junction transmembrane protein hardly detected in adult normal tissues, but aberrantly expressed in a variety of tumors, including ovarian cancer, testicular cancer, hepatocellular and lung adenocarcinoma. TJ-C64B is designed to conditionally activate T cells through 4-1BB stimulation upon CLDN6 engagement, positioning it as a potential novel immunotherapy for ovarian cancer and other CLDN6 positive tumors.
Details for the 2022 AACR presentations are as follows:
Abstract Title: |
Inhibition of B7-H3 by Enoblituzumab Elicits Anti-Tumor Immune Modulation in Both Innate and Adaptive Immunity |
Abstract #: |
4228 |
Presenting author: |
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Date and Time: |
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Summary:
- The function of B7-H3 and enoblituzumab in regulating immune response was investigated in human PBMCs using the Nanostring nCounter platform for gene expression and CyTOF mass cytometry for immunophenotyping.
- Data confirmed the immunosuppressive function of B7-H3 and demonstrated the immunoregulatory function of enoblituzumab as evidenced by the activation of cytolytic T cell and NK cells, reinvigoration of exhausted cells, and suppression of M2-like myeloid cells.
- Enoblituzumab exhibited tumor killing activity against ES-2, a B7-H3-expressing ovarian cancer cell line in vitro. Consistent with the enoblituzumab-associated increased 4-1BB expression in T and NK cells, activation of 4-1BB by urelumab, a 4-1BB agonist, further enhanced enoblituzumab-mediated tumor killing activity.
- These findings provide rationale for combination therapy with blockade of B7-H3 by enoblituzumab with other immunotherapies to achieve increased clinical efficacy against multiple cancer types.
Abstract Title: |
Discovery of a Novel Claudin 6 x 4-1BB Bispecific Antibody with Potent Anti-Tumor Activity through Conditional 4-1BB Activation |
Abstract #: |
5558 |
Presenting author: |
Jian Li, PhD |
Date and Time: |
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Summary:
- Data have confirmed the novel CLDN6-targeted 4-1BB bispecific antibody TJ-C64B to induce potent 4-1BB stimulation and anti-tumor activity in a CLDN6-dependent manner while minimizing the risk of liver toxicity.
- In humanized 4-1BB syngeneic mouse model, TJ-C64B exhibited significant tumor growth inhibition, associated with elevation in tumor infiltrating CD45 and CD8 cells as well as CD8/Treg ratio.
- From the safety perspective, there were no significant changes in liver enzymes following repeated TJ-C64B administration, suggesting a minimal risk for liver toxicity commonly induced by other 4-1BB agonist antibodies.
- Taken together, these data support further development of TJ-C64B towards clinical development subsequently.
About Enoblituzumab
Enoblituzumab is an investigational Fc-optimized monoclonal antibody that targets B7-H3, a member of the B7 family of immune regulator proteins. B7-H3 is widely expressed by many different tumor types and may play a key role in regulating the immune response to various types of cancer. Enoblituzumab has been or is currently being evaluated in clinical trials as a monotherapy or in combination with anti-PD-1-based therapies in patients with B7-H3-expressing cancers.
About TJ-C64B
TJ-C64B is a bispecific antibody simultaneously targeting tumor associated antigen Claudin 6 (CLDN6) and costimulatory molecule 4-1BB for CLDN6+ tumor treatment. TJ-C64B is specifically designed to conditionally activate T cells through 4-1BB stimulation upon CLDN6 engagement, providing a more localized activation of the immune system with good efficacy and reduced systemic toxicity. TJ-C64B is currently under preclinical development.
About
I-Mab Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding data from the enoblituzumab and TJ-C64B preclinical studies, the potential implications of clinical data for patients, and
I-Mab Contacts
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Investor Inquiries
E-mail: emilie@thepiacentegroup.com Office line: +86 21 6039 8363 |
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