Review of the recent clinical trials for PD-1/PD-L1 based lung cancer immunotherapy

Behrouzieh, Sadra; Sheida, Fateme; Rezaei, Nima

doi:10.1080/14737140.2021.1996230

Cited by 9 publications

(7 citation statements)

References 151 publications

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“…The concept of immunotherapy involves variety of approaches aimed at harnessing the immune system to target cancerous cells. The efficacy of these immune-based therapies is being actively evaluated in several clinical trials ( Behrouzieh et al., 2021 ; Juat et al., 2022 ; Liu et al., 2022 ) and has shown considerable promise in a number of human malignancies, for which immunotherapy is regarded as a standard of care.…”

Section: Introductionmentioning

confidence: 99%

Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer

Bulaon,

Khorattanakulchai,

Rattanapisit

et al. 2023

Front. Plant Sci.

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Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is an immune checkpoint regulator exclusively expressed on T cells that obstructs the cell’s effector functions. Ipilimumab (Yervoy®), a CTLA-4 blocking antibody, emerged as a notable breakthrough in modern cancer treatment, showing upfront clinical benefits in multiple carcinomas. However, the exhilarating cost of checkpoint blockade therapy is discouraging and even utmost prominent in developing countries. Thereby, affordability of cancer care has become a point of emphasis in drug development pipelines. Plant expression system blossomed as a cutting-edge platform for rapid, facile to scale-up, and economical production of recombinant therapeutics. Here, we describe the production of an anti-CTLA-4 2C8 antibody in Nicotiana benthamiana. ELISA and bio-layer interferometry were used to analyze antigen binding and binding kinetics. Anticancer responses in vivo were evaluated using knocked-in mice implanted with syngeneic colon tumor. At 4 days post-infiltration, the antibody was transiently expressed in plants with yields of up to 39.65 ± 8.42 μg/g fresh weight. Plant-produced 2C8 binds to both human and murine CTLA-4, and the plant-produced IgG1 also binds to human FcγRIIIa (V158). In addition, the plant-produced 2C8 monoclonal antibody is as effective as Yervoy® in inhibiting tumor growth in vivo. In conclusion, our study underlines the applicability of plant platform to produce functional therapeutic antibodies with promising potential in cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer

Bulaon,

Khorattanakulchai,

Rattanapisit

et al. 2023

Front. Plant Sci.

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“…Currently, the main focus of tumor immunotherapy lies on immune‐checkpoint inhibitors (ICIs), which targets the regulatory pathways of T cells and aims to enhance effector T cell toxicity by inhibiting the relevant immune checkpoints, thereby generating antitumor immune responses 44 . A variety of antibody‐based ICIs (e.g., pembrolizumab, nivolumab, and atezolizumab) have been approved by the U.S. FDA for the combination treatment of melanoma and non‐small cell lung cancer (NSCLC) 45 . Immunotherapy has led to long‐term remission in some patients and no recurrence for many years.…”

Section: Hypoxia Plays Important Roles In Various Antitumor Therapiesmentioning

confidence: 99%

“…44 A variety of antibodybased ICIs (e.g., pembrolizumab, nivolumab, and atezolizumab) have been approved by the U.S. FDA for the combination treatment of melanoma and non-small cell lung cancer (NSCLC). 45 Immunotherapy has led to longterm remission in some patients and no recurrence for many years. However, according to research data, ICIs are effective in only 20%-40% of cancer patients, and in about a third of patients whose ICI treatments are initially effective, but tumors eventually progress or recur.…”

Section: Immunotherapymentioning

confidence: 99%

Positron emission tomography imaging sheds new light on hypoxia and antitumor therapies

Fang

Wang

Lan

et al. 2023

Interdisciplinary Medicine

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The effect of the hypoxic tumor microenvironment (TME) on the effectiveness of cancer treatments has received widespread attention. It is crucial to investigate the mechanisms by which hypoxia influences the efficacy of these treatments in order to improve the therapeutic outcomes for malignant tumors and the prognoses of patients. Positron emission tomography (PET) imaging is a non-invasive, reproducible, and quantitative imaging technique that can visualize molecular biological changes in vivo. By utilizing specific PET probes, it is possible to both depict in vivo oxygen levels within the TME and evaluate cancer treatment effectiveness at various targets. This review summarizes the effect of hypoxia on various cancer treatments and examines the role of PET imaging in understanding the mechanisms of hypoxia during and after cancer treatments. It is anticipated that this review will provide new insights for improving tumor therapy from the hypoxia perspective and for early prediction and assessment of therapeutic efficacy via PET imaging.

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“…Tumor cells can escape the killing of tumor cells by T cells through downregulating MHC and upregulating the expression of inhibitory receptors such as PD-L1, CTLA-4, LAG-3, TIM-3 and TIGIT ( 32 – 34 ), and blocking the binding of these inhibitory receptors to ligands can restore T-cell anti-tumor activity ( 35 ). PD-1/PD-L1 monoclonal antibodies (mAbs) demonstrate significant anti-tumor effect and prolong overall survival (OS) in various malignancies ( 36 – 38 ). PD-1 is an immunosuppressive receptor that is highly expressed on TILs ( 35 ), whereas PD-L1 as the main ligand of PD-1 is highly expressed on the surface of tumor cells ( 39 ).…”

Section: Pd-1/pd-l1mentioning

confidence: 99%

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

et al. 2022

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Gastric cancer (GC) is a malignancy with a high incidence and mortality, and the emergence of immunotherapy has brought survival benefits to GC patients. Compared with traditional therapy, immunotherapy has the advantages of durable response, long-term survival benefits, and lower toxicity. Therefore, targeted immune cells are the most promising therapeutic strategy in the field of oncology. In this review, we introduce the role and significance of each immune cell in the tumor microenvironment of GC and summarize the current landscape of immunotherapy in GC, which includes immune checkpoint inhibitors, adoptive cell therapy (ACT), dendritic cell (DC) vaccines, reduction of M2 tumor-associated macrophages (M2 TAMs), N2 tumor-associated neutrophils (N2 TANs), myeloid-derived suppressor cells (MDSCs), effector regulatory T cells (eTregs), and regulatory B cells (Bregs) in the tumor microenvironment and reprogram TAMs and TANs into tumor killer cells. The most widely used immunotherapy strategies are the immune checkpoint inhibitor programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T lymphocyte–associated protein 4 (CTLA-4) antibody, and chimeric antigen receptor T (CAR-T) in ACT, and these therapeutic strategies have significant anti-tumor efficacy in solid tumors and hematological tumors. Targeting other immune cells provides a new direction for the immunotherapy of GC despite the relatively weak clinical data, which have been confirmed to restore or enhance anti-tumor immune function in preclinical studies and some treatment strategies have entered the clinical trial stage, and it is expected that more and more effective immune cell–based therapeutic methods will be developed and applied.

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Review of the recent clinical trials for PD-1/PD-L1 based lung cancer immunotherapy

Cited by 9 publications

References 151 publications

Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer

Antitumor effect of plant-produced anti-CTLA-4 monoclonal antibody in a murine model of colon cancer

Positron emission tomography imaging sheds new light on hypoxia and antitumor therapies

Therapeutic strategies for gastric cancer targeting immune cells: Future directions

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