Precision Biologics will present affinity maturation and characterization of a novel core 2 O-glycan epitope targeting anti-human carcinoma mAb PB-223 at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024
BETHESDA, Md., Nov. 6, 2024 /PRNewswire/ -- Precision Biologics, Inc. reports that affinity maturation and characterization of its novel anti-core 2 O-glycan monoclonal antibody PB-223, will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024, George R. Brown Convention Center, Houston, Texas, USA, Poster title: Affinity Maturation and Characterization of a Novel O-glycan Epitope Targeting
Anti-Human Carcinoma Monoclonal Antibody (mAb) PB-223
Presentation of the poster will be made in person on the following dates and locations:
- November 7th, 2024: SITC Immune Engineering Workshop, 3.10 p.m-5 p.m. CST, George R. Brown Convention Center, Level 3 - Grand Ballroom AB, Houston, Texas, USA
- November 8th, 2024: Poster Session Immuno-Engineering, abstract number 1101, 12:15–1:45 p.m. CST and 5:30-7 p.m. CST, George R. Brown Convention Center, Level 1-Exhibit Halls A B, Houston, Texas, USA
BACKGROUND:
PB-223 is an innovative mAb developed through immune engineering from the chimeric IgG1 NEO-102 (Ensituximab). It targets a unique core 2 O-glycan (variant of MUC5AC),
Preclinical and clinical data showed that NEO-102 specifically binds to and kills colorectal and pancreatic cancer cells through ADCC. NEO-102 did not bind to healthy tissues. In a phase 2 study, NEO-102 showed promising results in heavily pretreated patients with advanced, refractory metastatic colorectal cancer.
In general, the efficacy of using a monoclonal antibody as a single agent in cancer immunotherapy can be impaired not only by the resistance of cancer cells in the tumor microenvironment (TME), but also by a low binding affinity to target antigens expressed on cancer cells.
- One strategy to improve the therapeutic efficacy of monoclonal antibodies is to enhance their binding affinity to target antigens.
STUDY PRESENTED AT SITC 2024:
- The objective of this study was to enhance the binding affinity of NEO-102 to its target antigen. By engineering the VH and VL sequences of NEO-102 through Fast Screening for Expression Biophysical Properties and Affinity (FASEA), while maintaining the binding specificity to the target antigen, allowed us to develop a new clone with a lower KD and markedly improved characteristics. This new biologic asset developed by affinity maturation was given the name PB-223.
- Binding kinetics of PB-223 and NEO-102 to the target antigen were compared by ELISA. Results show that PB-223 has a KD of 4.5-fold less than NEO-102, suggesting a higher affinity for the target antigen by PB-223 compared to NEO-102.
- The binding affinity of PB-223 and NEO-102 to various human tumor cell lines was also evaluated by flow cytometry. Flow cytometry analysis showed that PB-223 not only has markedly enhanced comparative binding to colorectal and pancreatic cancer cell lines recognized by NEO-102, but that PB-223 is also able to bind to many additional tumor cell lines that were not recognized by NEO-102.
- Further study by O-glycan array analysis showed that 1) PB-223 binds specifically to core-2 O-glycans, and that 2) core 2 O-glycans recognized by PB-223 are expressed on tumor cell lines positive for PB-223 binding in flow cytometry.
- Immunohistochemistry (IHC) analysis performed on human tumor tissues shows that PB-223 does not bind to healthy tissues. IHC analysis also shows that PB-223, in addition to binding to both colorectal cancer and pancreatic cancer, it also binds to additional tumor tissues not reactive with NEO-102, including triple negative breast cancer, prostate cancer, kidney cancer, head and neck cancer, liver cancer, and bladder cancer.
- In addition, this study demonstrated that PB-223 is internalized into human cancer cell lines expressing core 2 O-glycans.
Findings from this study suggest that PB-223 has a strong binding affinity for human cancers expressing core 2 O-glycans and that PB-223 may be a potential candidate for the development of antibody-drug conjugates (ADC) for treatment of various human carcinomas.
The PDF of the poster will be available starting from November 5, 2024, at the following link: https://precision-biologics.com/wp-content/uploads/SITC-2024-POSTER-36X72-inches-final.pdf
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SOURCE Precision Biologics
