Bispecific antibodies engage T cells for antitumor immunotherapy

@article{Choi2011BispecificAE,
  title={Bispecific antibodies engage T cells for antitumor immunotherapy},
  author={Bryan D Choi and Mingqin Cai and Darell D. Bigner and Ankit I. Mehta and C T Kuan and John H. Sampson},
  journal={Expert Opinion on Biological Therapy},
  year={2011},
  volume={11},
  pages={843 - 853}
}
Introduction: Although considerable evidence supports the hypothesis that T cells play a critical role in the immune response against cancer, the ability to mount and sustain tumor-specific cellular responses in vivo remains a challenge. A strategy that harnesses the cytotoxic advantage of T cell therapy is the use of bispecific antibodies designed to engage and activate endogenous polyclonal T cell populations via the CD3 complex, but only in the presence of a tumor antigen. While antibody… 
View on Taylor & Francis
braintumor.org
74 Citations
Highly Influential Citations
2
Background Citations
31
Methods Citations
1
Results Citations
1

74 Citations

Citation Type

Citation Type

Novel immunotherapies for hematologic malignancies
TLDR
Novel strategies that exploit the patient's immune system to kill cancer are appraise by suggesting multi‐prong approaches to improve treatment outcomes and curative responses in patients.
Arming oncolytic viruses to leverage antitumor immunity
TLDR
A combination of trans-genes encoding bispecific T-cell engagers, immune checkpoint blockers and antigen-presenting cell enhancers will remove suppressive hurdles in the TME and allow for optimal antitumor efficacy of armed OVs.
Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies
TLDR
This review will focus on the state-of-the art, the design, and the exploitation of bsAbs against solid malignancies, delineating their mechanisms of action, major pitfalls, and future directions.
A new class of bispecific antibodies to redirect T cells for cancer immunotherapy
TLDR
The generation, by the modular DOCK-AND-LOCKTM (DNLTM) method, of novel T-cell redirecting bispecific antibodies, each comprising a monovalent anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs are described.
Arming oncolytic viruses to leverage antitumor immunity
TLDR
The different options to modulate immune suppression in the tumor microenvironment (TME) and to facilitate the generation of effective antitumor responses that have been investigated in conjunction with OVs in recent years are explored.
Bispecific antibodies: an innovative arsenal to hunt, grab and destroy cancer cells.
TLDR
An overview of the established bsAbs focusing on improvements in format and design as well as the mechanisms of action of the most promising candidates is provided and the results of the the most recent clinical studies are described.
Human Regulatory T Cells Kill Tumor Cells through Granzyme-Dependent Cytotoxicity upon Retargeting with a Bispecific Antibody
TLDR
Analysis of human primary glioblastoma also displayed diffused infiltration of granzyme-expressing FoxP3+ T cells, suggesting that despite their known suppressive functions, tumor-infiltrating Tregs possess potent cytotoxic mechanisms that can be co-opted for efficient tumor cell lysis.
Targeting T cells to tumor cells using bispecific antibodies.
Immunotargeting and therapy of cancer by advanced multivalence antibody scaffolds
TLDR
The avidity and multivalency of monoclonal antibodies is discussed and comprehensive insights into advanced Ab scaffolds used for immunotargeting and therapy of cancer are provided.
Investigating functions of tumor-infiltrating natural killer cells in genetically-engineered mouse models of non-small cell lung cancer
TLDR
It is hypothesized that strategies for stimulating NK cells in tumors may enhance the efficacy of T cell-targeted therapies in the treatment of cancer, and a novel immunotherapeutic molecule for stimulatingNK cell responses against cancer cells is developed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 108 REFERENCES
Bispecific T-cell engaging antibodies for cancer therapy.
TLDR
The principle of a new class of bispecific antibodies called BiTE (for "bispecific T-cell engager") antibodies is reviewed, suggesting that this therapeutic paradigm is finally showing promise for treatment of both bulky and minimal residual disease.
BiTE: Teaching antibodies to engage T-cells for cancer therapy.
TLDR
Clinical activity of BiTE antibodies corroborates findings that ex vivo expanded, autologous T-cells derived from tumor tissue, or transfected with specific T-cell receptors, have shown therapeutic potential in the treatment of solid tumors.
Bispecific anti-idiotype/anti-CD3 antibody therapy of murine B cell lymphoma.
TLDR
It is demonstrated bispecific IgG-directed lysis is therapeutically superior to monospecific anti-Id therapy in the 38C13 tumor model, and that tumorLysis is mediated largely by cell-cell contact.
Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Cancer
TLDR
Clinical trials revealed that the adoptive transfer of T cells engineered with first generation CARs represents a feasible concept for the induction of clinical responses in some tumor patients, however, further improvement is required, which may be achieved by second or third generation CAR-engrafted T cells.
Hybrid antibodies can target sites for attack by T cells
TLDR
It is shown that heteroconjugates of monoclonal antibodies (referred to hereafter as hybrid antibodies), in which one of the component binding sites is anti-T-cell receptor and the other component binding site is directed against any chosen target antigen, can focus T cells to act at the targeted site.
Strictly target cell-dependent activation of T cells by bispecific single-chain antibody constructs of the BiTE class.
Human ovarian carcinoma lysis by cytotoxic t cells targeted by bispecific monoclonal antibodies: Analysis of the antibody components
TLDR
Analysis of the bispecific reagents indicated that hybrid MAbs are superior to the heteroconjugate as far as storage stability is concerned, and human immunoglobulins were unable to compete with the Fc receptor binding of the hybridMAbs and therefore, Fc fragment removal seems to be an essential step.
Bispecific antibody-mediated immunotherapy of the BCL1 lymphoma: increased efficacy with multiple injections and CD28-induced costimulation.
TLDR
The results suggest that the BSAB and CD28 combination was able to activate memory and effector T cells and to focus them on the tumor, but was unable to activate naive T cells fully.
Potent inhibition of local and disseminated tumor growth in immunocompetent mouse models by a bispecific antibody construct specific for Murine CD3
TLDR
This study shows that bispecific single-chain antibody construct BiTEs also have a high antitumor activity in immunocompetent mice and that there is no obvious need for costimulation of T cells by secondary agents.
MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors.
...
1
2
3
4
5
...