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Antibody–drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance

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Abstract

An antibody–drug conjugate (ADC) is an advanced chemotherapeutic option with immense promises in treating many tumor. They are designed to selectively attack and kill neoplastic cells with minimal toxicity to normal tissues. ADCs are complex engineered immunoconjugates that comprise a monoclonal antibody for site-directed delivery and cytotoxic payload for targeted destruction of malignant cells. Therefore, it enables the reduction of off-target toxicities and enhances the therapeutic index of the drug. Hepatocellular carcinoma (HCC) is a solid tumor that shows high heterogeneity of molecular phenotypes and is considered the second most common cause of cancer-related death. Studies show enormous potential for ADCs targeting GPC3 and CD24 and other tumor-associated antigens in HCC with their high, selective expression and show potential outputs in preclinical evaluations. The review mainly highlights the preclinical evaluation of different antigen-targeted ADCs such as MetFab-DOX, Anti-c-Met IgG-OXA, Anti CD 24, ANC–HN-01, G7mab-DOX, hYP7-DCand hYP7-PC, Anti-CD147 ILs-DOX and AC133-vcMMAF against hepatocellular carcinoma and its future relevance.

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Acknowledgements

We acknowledge the support from Amrita VishwaVidyapeetham. We express our sincere gratitude to Dr Shanthikumar. V. Nair, Dean of Research, Amrita Vishwa Vidyapeetham and Dr Sabitha M, Principal, Amrita School of Pharmacy for the encouragement, support and all the facilities provided.

Funding

We acknowledge the support of the Amrita Vishwa Vidyapeetham PG student fellowship to MM. The work is partially supported by Amrita Vishwa Vidyapeetham faculty SEED grant to LRN (K-PHAR-20-627).

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Author notes

  1. Maneesha Murali and Ayana R. Kumar these authors contributed equally.

Authors and Affiliations

  1. Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P. O., Kochi, Kerala, 682041, India

    M. Murali, A. R. Kumar, B. Nair, A. R. Devan, G. K. Pradeep & L. R. Nath

  2. Department of Medical Oncology and Hematology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, 682041, India

    K. Pavithran

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  1. M. Murali
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  2. A. R. Kumar
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  3. B. Nair
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  4. K. Pavithran
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  5. A. R. Devan
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  6. G. K. Pradeep
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  7. L. R. Nath
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Contributions

LRN designed, conceptualized and writing the review. PK revised and proofread the manuscript. MM, ARK and ARD carried out a literature survey and writing. BLN and GP contributed to the artwork.

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Correspondence to L. R. Nath.

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Murali, M., Kumar, A.R., Nair, B. et al. Antibody–drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance. Clin Transl Oncol 24, 407–431 (2022). https://doi.org/10.1007/s12094-021-02707-5

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