Beyond direct killing—novel cellular immunotherapeutic strategies to reshape the tumor microenvironment

Huynh, Duc; Winter, Pia; Märkl, Florian; Endres, Stefan; Kobold, Sebastian

doi:10.1007/s00281-022-00962-4

Cited by 10 publications

(8 citation statements)

References 111 publications

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“…CAR-T technology has developed rapidly in recent years and is one of the most promising strategies in cancer therapy (87). Rousso-Noori et al designed gC1qR CAR T cells in glioma after confirming that gC1qR was expressed in mice and human glioma.…”

Section: Potential For Translating Into Clinic Advances In Preclinica...mentioning

confidence: 99%

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gC1qR: A New Target for Cancer Immunotherapy

Lei

Qin

et al. 2023

Front. Immunol.

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Although breakthroughs in cancer treatment have been achieved, immunotherapy yields only modest benefits in most patients. There is still a gap in clarifying the immune evasiveness and immune-resistance mechanisms. Identifying other candidate targets for cancer immunotherapy is therefore a clear unmet clinical need. The complement system, a pillar of innate immunity, has recently entered the limelight due to its immunoregulatory functions in the tumor microenvironment (TME). In particular, gC1qR, a receptor for globular heads of C1q, serves as a promising new target and has attracted more attention. gC1qR, also named P32/C1qBP/HABP1, is a multifunctional protein that is overexpressed in various cancers and holds prognostic value. It regulates the tumorigenic, progression and metastatic properties of tumor cells through several downstream signaling pathways, including the Wnt/β-catenin, PKC–NF-κB and Akt/PKB pathways. A few preclinical experiments conducted through gC1qR interventions, such as monoclonal antibody, chimeric antigen receptor T‐cell (CAR‐T) therapy, and tumor vaccination, have shown encouraging results in anticancer activity. The efficacy may rely on the regulatory role on the TME, induction of tumor cells apoptosis and antiangiogenic activity. Nevertheless, the current understanding of the relationship between cancer immunotherapy and gC1qR remains elusive and often contradictory, posing both opportunities and challenges for therapeutic translation in the clinic. In this review, we focus on the current understanding of gC1qR function in cancer immunology and highlight the vital roles in regulating the TME. We also examines the rationale behind targeting gC1qR and discusses the potential for translating into clinical practice.

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Section: Potential For Translating Into Clinic Advances In Preclinica...mentioning

confidence: 99%

“…CAR-T technology has developed rapidly in recent years and is one of the most promising strategies in cancer therapy ( 87 ). Rousso-Noori et al.…”

Section: Potential For Translating Into Clinicmentioning

confidence: 99%

gC1qR: A New Target for Cancer Immunotherapy

Lei

Qin

et al. 2023

Front. Immunol.

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“…This approach provides a very simple mechanism to dramatically change the dynamics of TCR-T cell responses to tumor cells. Other variations of switch proteins are in development for use in TCR-T therapies that utilize different external binding domains or internal signaling pathways to mobilize cytokine production or amplify multiple effector cell activities in TCR-T cells (149)(150)(151)(152).…”

Section: Impacts Of the Tme On Trafficking And Function Of T Cells An...mentioning

confidence: 99%

“…A dramatic impingement of TCR-T cell function is observed by repetitive exposure to tumor cells ( 83 , 146 ). This occurs because the tumor cells express pHLA ligands that signal the TCR but they lack ligands required for T cell costimulation, via the CD28 or CD137 (41BB) pathway ( 146 , 148 , 149 ). As a result, repetitive exposure of TCR-T cells leads to metabolic stress and exhaustion ( 83 , 148 , 149 ).…”

Section: Module 3: Tcr-t Therapy Optimizationmentioning

confidence: 99%

“…This occurs because the tumor cells express pHLA ligands that signal the TCR but they lack ligands required for T cell costimulation, via the CD28 or CD137 (41BB) pathway ( 146 , 148 , 149 ). As a result, repetitive exposure of TCR-T cells leads to metabolic stress and exhaustion ( 83 , 148 , 149 ). Thereby, tumor cells cause demise of TCR-T cell function through two combined mechanisms – signaling of rTCR by tumor cell-associated pHLA complexes in the absence of costimulation and engagement of the PD-1 inhibitory pathway through expression of PD-L1.…”

Section: Module 3: Tcr-t Therapy Optimizationmentioning

confidence: 99%

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Evolution by innovation as a driving force to improve TCR-T therapies

Schendel

2023

Front. Oncol.

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Adoptive cell therapies continually evolve through science-based innovation. Specialized innovations for TCR-T therapies are described here that are embedded in an End-to-End Platform for TCR-T Therapy Development which aims to provide solutions for key unmet patient needs by addressing challenges of TCR-T therapy, including selection of target antigens and suitable T cell receptors, generation of TCR-T therapies that provide long term, durable efficacy and safety and development of efficient and scalable production of patient-specific (personalized) TCR-T therapy for solid tumors. Multiple, combinable, innovative technologies are used in a systematic and sequential manner in the development of TCR-T therapies. One group of technologies encompasses product enhancements that enable TCR-T therapies to be safer, more specific and more effective. The second group of technologies addresses development optimization that supports discovery and development processes for TCR-T therapies to be performed more quickly, with higher quality and greater efficiency. Each module incorporates innovations layered onto basic technologies common to the field of immunology. An active approach of “evolution by innovation” supports the overall goal to develop best-in-class TCR-T therapies for treatment of patients with solid cancer.

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Novel immunotherapeutic combinations moving forward: the modulation of the immunosuppressive microenvironment

Andersen

2023

Semin Immunopathol

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Beyond direct killing—novel cellular immunotherapeutic strategies to reshape the tumor microenvironment

Cited by 10 publications

References 111 publications

gC1qR: A New Target for Cancer Immunotherapy

gC1qR: A New Target for Cancer Immunotherapy

Evolution by innovation as a driving force to improve TCR-T therapies

Novel immunotherapeutic combinations moving forward: the modulation of the immunosuppressive microenvironment

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