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Related Concept Videos

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Updated: May 2, 2026

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
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Engineering functionality-optimized fully human B7-H3 CAR T cells for enhanced solid tumor therapy.

Pradip Bajgain1, Yang Feng1, Mariela Puebla2

  • 1Tumor Angiogenesis Unit, Mouse Cancer Genetics Program, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Frederick, MD 21702, USA.

Cell Reports. Medicine
|April 30, 2026
PubMed
Summary
This summary is machine-generated.

A novel fully human B7-H3 specific antibody fragment, Y111, shows superior efficacy in preclinical models. This breakthrough offers improved chimeric antigen receptor (CAR) T cell therapy for solid tumors, overcoming limitations of existing treatments.

Keywords:
B7-H3B7H3CARCD276adoptive T cell transferchimeric antigen receptorfully human antibodyglioblastomaneuroblastomapancreatic ductal adenocarcinomaphage display library

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Area of Science:

  • Oncology
  • Immunotherapy
  • Biotechnology

Background:

  • B7-H3 is a cell surface protein frequently overexpressed in solid tumors.
  • Current chimeric antigen receptor (CAR) T cell therapies targeting B7-H3 utilize murine-derived antibodies, risking immune rejection.
  • Existing humanized CARs may still contain immunogenic residues.

Purpose of the Study:

  • To develop fully human single-chain variable fragments (scFvs) for B7-H3 CAR T cell therapy.
  • To evaluate the safety and efficacy of a novel human B7-H3 CAR T cell therapy in preclinical cancer models.

Main Methods:

  • In vitro phage display was used to generate fully human B7-H3-specific scFvs.
  • CAR T cells incorporating the lead human binder, Y111, were tested in pancreatic cancer, neuroblastoma, and glioblastoma xenograft models.
  • Comparative analysis with existing B7-H3 CARs (376.96 and MGA271) was performed.

Main Results:

  • CAR T cells with the Y111 binder were well-tolerated in xenograft models.
  • Y111-based CAR T cells demonstrated superior antitumor activity compared to murine-derived CARs.
  • Complete tumor responses, rejection, and significant survival benefits were observed with Y111 CAR treatment.

Conclusions:

  • The fully human B7-H3 binder Y111 is a promising candidate for next-generation CAR T cell therapy.
  • Y111 CAR T cells offer enhanced safety and efficacy for treating solid tumors.
  • This approach overcomes immunogenicity issues associated with non-human CAR components.