Clinically approved combination immunotherapy: Current status, limitations, and future perspective

Lu, Ligong; Zhan, Meixiao; Li, Xian-Yang; Zhang, Hui; Dauphars, Danielle J.; Jiang, Jun; Yin, Hua; Li, Shiyou; Luo, Sheng; Li, Yong; He, You–Wen

doi:10.1016/j.crimmu.2022.05.003

Cited by 41 publications

(18 citation statements)

References 116 publications

(207 reference statements)

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“…Lastly, we found that combination of mGT103 with anti-PD-L1 and the immune adjuvant poly(I:C) exhibit strong antitumor e cacy. To date, there are 35 FDA approved combination immunotherapies for various types of cancer 42 . The combination immunotherapies for NSCLC primarily consists of anti-PD-1/PD-L1 mAbs plus chemotherapies 42 .…”

Section: Discussionmentioning

confidence: 99%

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Creation of a Favorable Antitumor Microenvironment by the Anti-Complement Factor H Antibody GT103

Saxena

Bushey

Campa

et al. 2022

Preprint

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Complement factor H (CFH) is an abundant serum protein regulating complement activation and protecting host cells from attack by the alternative pathway of complement mediated cytotoxicity. We previously identified an anti-CFH autoantibody in early stage NSCLC patients, and cloned from single peripheral B cells a lead therapeutic mAb, GT103, for cancer immunotherapy. Although GT103 has potent antitumor activities, the underlying antitumor mechanisms remain unknown. Herein we investigated GT103-mediated antitumor effects and demonstrate that GT103 enhances antitumor immunity through multiple pathways. GT103 treatment creates a favorable tumor microenvironment (TME) by decreasing immunosuppressive regulatory T cells and myeloid-derived suppressor cells and enhancing antigen-specific effector T cells and has a synergistic antitumor effect with anti-PD-L1 mAb. Furthermore, the immune landscape of tumors from early stage patients expressing the anti-CFH autoantibody is associated with an immunologically active TME. Our results provide novel mechanistic insights into this promising human-derived immunotherapeutic agent, which is currently undergoing a Phase I/II clinical trial in patients with NSCLC.

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Section: Discussionmentioning

confidence: 99%

“…To date, there are 35 FDA approved combination immunotherapies for various types of cancer 42 . The combination immunotherapies for NSCLC primarily consists of anti-PD-1/PD-L1 mAbs plus chemotherapies 42 . Our current phase I/II clinical trial is to treat advanced stage NSCLC patients with GT103 alone (NCT04314089).…”

Section: Discussionmentioning

confidence: 99%

Creation of a Favorable Antitumor Microenvironment by the Anti-Complement Factor H Antibody GT103

Saxena

Bushey

Campa

et al. 2022

Preprint

Self Cite

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“…As it stands, most approved combination immunotherapies largely rely on a combination of immune checkpoint inhibitors (ICIs) and have emerged as first-line treatments for several major cancer types ( 191 ). The future of combination immunotherapies with γδT cells likely extends beyond ICI-based approaches, aiming for control and eradication of established tumors.…”

Section: Engineering Strategies: the Advances And Advantages Of γδT C...mentioning

confidence: 99%

Advancements in γδT cell engineering: paving the way for enhanced cancer immunotherapy

Yuan,

Wang,

Hawes

et al. 2024

Front. Immunol.

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Comprising only 1-10% of the circulating T cell population, γδT cells play a pivotal role in cancer immunotherapy due to their unique amalgamation of innate and adaptive immune features. These cells can secrete cytokines, including interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), and can directly eliminate tumor cells through mechanisms like Fas/FasL and antibody-dependent cell-mediated cytotoxicity (ADCC). Unlike conventional αβT cells, γδT cells can target a wide variety of cancer cells independently of major histocompatibility complex (MHC) presentation and function as antigen-presenting cells (APCs). Their ability of recognizing antigens in a non-MHC restricted manner makes them an ideal candidate for allogeneic immunotherapy. Additionally, γδT cells exhibit specific tissue tropism, and rapid responsiveness upon reaching cellular targets, indicating a high level of cellular precision and adaptability. Despite these capabilities, the therapeutic potential of γδT cells has been hindered by some limitations, including their restricted abundance, unsatisfactory expansion, limited persistence, and complex biology and plasticity. To address these issues, gene-engineering strategies like the use of chimeric antigen receptor (CAR) T therapy, T cell receptor (TCR) gene transfer, and the combination with γδT cell engagers are being explored. This review will outline the progress in various engineering strategies, discuss their implications and challenges that lie ahead, and the future directions for engineered γδT cells in both monotherapy and combination immunotherapy.

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“…However, clinical implementation of immunotherapy is still challenged by low response rate and off-target risks, especially during systemic administration of the immunotherapeutics. , In addition, single-mode immunotherapy is often insufficient to maintain a sustained “cancer-immunity cycle” for robust antitumor immune responses, in large part due to the multiple immunosuppressive factors within the tumor microenvironment (TME) . Hence, TME regulation methods and combination immunotherapy strategies have been widely investigated in preclinical and clinical trials. , …”

Section: Introductionmentioning

confidence: 99%

“…4 Hence, TME regulation methods and combination immunotherapy strat-egies have been widely investigated in preclinical and clinical trials. 5,6 The rapid development in nanoscale drug delivery systems tion with other therapeutic modalities. 7−9 NDDSs with the help of diverse nanomaterials may facilitate highly efficient and precise delivery of antigen, adjuvants, and other immune-active compounds into tumors or lymphoid tissues, 10,11 thereby reducing side toxicities with enhanced immune responses.…”

Section: Introductionmentioning

confidence: 99%

Manganese Dioxide-Entrapping Dendrimers Co-Deliver Protein and Nucleotide for Magnetic Resonance Imaging-Guided Chemodynamic/Starvation/Immune Therapy of Tumors

Gao,

Ouyang,

Shen

et al. 2023

ACS Nano

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Clinically approved combination immunotherapy: Current status, limitations, and future perspective

Cited by 41 publications

References 116 publications

Creation of a Favorable Antitumor Microenvironment by the Anti-Complement Factor H Antibody GT103

Creation of a Favorable Antitumor Microenvironment by the Anti-Complement Factor H Antibody GT103

Advancements in γδT cell engineering: paving the way for enhanced cancer immunotherapy

Manganese Dioxide-Entrapping Dendrimers Co-Deliver Protein and Nucleotide for Magnetic Resonance Imaging-Guided Chemodynamic/Starvation/Immune Therapy of Tumors

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