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Immune checkpoint inhibitors and cancer immunotherapy by aptamers: an overview

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Abstract

Efforts in cancer immunotherapy aim to counteract evasion mechanisms and stimulate the immune system to recognise and attack cancer cells effectively. Combination therapies that target multiple aspects of immune evasion are being investigated to enhance the overall efficacy of cancer immunotherapy. PD-1 (Programmed Cell Death Protein 1), CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4), LAG-3 (Lymphocyte-Activation Gene 3), and TIM-3 (T Cell Immunoglobulin and Mucin Domain-Containing Protein3) are all immune checkpoint receptors that play crucial roles in regulating the immune response and maintaining self-tolerance often exploited by cancer cells to evade immune surveillance. Antibodies targeted against immune checkpoint inhibitors such as anti-PD-1 antibodies (e.g., pembrolizumab, nivolumab), anti-CTLA-4 antibodies (e.g., Ipilimumab), and experimental drugs targeting LAG-3 and TIM-3, aim to block these interactions and unleash the immune system’s ability to recognise and destroy cancer cells. The US FDA has approved different categories of immune checkpoint inhibitors that have been utilised successfully in some patients with metastatic melanoma, renal cell carcinoma, head and neck cancers, and non-small lung cancer. Although several immune checkpoint inhibitor antibodies have been developed, they exhibited immune-related adverse effects, resulting in hypophysitis, diabetes, and neurological issues. These adverse effects of antibodies can be reduced by developing aptamer against the target. Aptamers offer several advantages over traditional antibodies, such as improved specificity, reduced immunogenicity, and flexible design for reduced adverse effects that specifically target and block protein–protein or receptor-ligand interactions involved in immune checkpoint pathways. The current study aims to review the function of particular immune checkpoint inhibitors along with developed aptamer-mediated antitumor cytotoxicity in cancer treatment.

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Abbreviations

PD-1:

Programmed cell death 1

CTLA-4:

Cytotoxic T lymphocyte-associated protein 4

LAG-3:

Lymphocyte-Activation Gene 3

PD-L1:

Programmed cell death ligand1

PD-L2:

Programmed cell death ligand2

TIM-3:

T cell immunoglobulin and mucin-domain containing-3

FDA:

Food and Drug Administration

IARC:

International Agency for Research on Cancer

ICIs:

Immune checkpoint Inhibitors

NSCLC:

Non-small cell lung cancer

VISTA:

V-domain Ig suppressor of T cell activation

BTLA:

B and T cell lymphocyte attenuator

TIGIT:

T cell immunoglobulin and ITIM domain

B7-H3:

B7 homolog 3 protein

APCs:

Antigen Presenting Cells

TME:

Tumour Microenvironment

TCR:

T-cell receptor

HAVCR2:

Hepatitis A virus cellular receptor 2

mAbs:

Monoclonal Antibodies

IbAEs:

Immune-based adverse events

SELEX:

Systemic Evolution of Ligands by Exponential Enrichment

VEGF:

Vascular Endothelial Growth Factor

IDO:

Indoleamine 2,3-dioxygenase

DCs:

Dendritic cells

NKCs:

Natural Killer Cells

MHC II:

Major Histocompatibility Complex II

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  1. Department of Biotechnology, School of Bioengineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603203, India

    Priyatharcini Kejamurthy & K. T. Ramya Devi

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Both authors have contributed to this manuscript, and KTR gave the outline of it. Later, the data collection and manuscript preparation was done by PKM. KTR did the final part and evaluation. Both authors commented on and approved the final manuscript.

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Kejamurthy, P., Devi, K.T.R. Immune checkpoint inhibitors and cancer immunotherapy by aptamers: an overview. Med Oncol 41, 40 (2024). https://doi.org/10.1007/s12032-023-02267-4

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