The current socioeconomic and regulatory landscape of immune effector cell therapies

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells....

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Main Authors: Chiranjeevi Sainatham, Devvrat Yadav, Aravind Dilli Babu, Jayanth Reddy Tallapalli, Sai Gautham Kanagala, Evgenii Filippov, Franco Murillo Chavez, Nausheen Ahmed, Forat Lutfi
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2024.1462307/full
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author Chiranjeevi Sainatham
Devvrat Yadav
Aravind Dilli Babu
Jayanth Reddy Tallapalli
Sai Gautham Kanagala
Evgenii Filippov
Franco Murillo Chavez
Nausheen Ahmed
Forat Lutfi
author_facet Chiranjeevi Sainatham
Devvrat Yadav
Aravind Dilli Babu
Jayanth Reddy Tallapalli
Sai Gautham Kanagala
Evgenii Filippov
Franco Murillo Chavez
Nausheen Ahmed
Forat Lutfi
author_sort Chiranjeevi Sainatham
collection DOAJ
description Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T cells to recognize intracellular tumor antigens presented by major histocompatibility complex (MHC) molecules, offer promise for a range of solid tumors. NK-cell therapies leverage NK cells’ innate cytotoxicity, providing an allogeneic approach that avoids some of the immune-related complications associated with T-cell-based therapies. Macrophage-based therapies, still in early stages of the development, focus on reprogramming macrophages to stimulate an immune response against cancer cells in the tumor microenvironment. Despite their promise, socioeconomic and regulatory challenges hinder the accessibility and scalability of immune cell effector therapies. These treatments are costly, with CAR-T therapies currently exceeding $400,000 per patient, creating significant disparities in access based on socioeconomic status and geographic location. The high manufacturing costs stem from the personalized, labor-intensive processes of harvesting, modifying, and expanding patients’ cells. Moreover, complex logistics for manufacturing and delivering these therapies limit their reach, particularly in low-resource settings. Regulatory pathways further complicate the landscape. In the United States., the Food and Drug Administrations’ (FDA) accelerated approval processes for cell-based therapies facilitate innovation but do not address cost-related barriers. In Europe, the European Medicines Agency (EMA) offers adaptive pathways, yet decentralized reimbursement systems create uneven access across member states. Additionally, differing regulatory standards for manufacturing and quality control worldwide pose hurdles for global harmonization and access. To expand the reach of immune effector cell therapies, a multipronged approach is needed—streamlined regulatory frameworks, policies to reduce treatment costs, and international collaborations to standardize manufacturing. Addressing these socioeconomic and regulatory obstacles is essential to make these life-saving therapies accessible to a broader patient population worldwide. We present a literature review on the current landscape of immune effector cell therapies and barriers of access to currently approved standard of care therapy at various levels.
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spelling doaj-art-f0abd05f4a5f47ad88dca18090e29d192024-12-04T04:31:35ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-12-011110.3389/fmed.2024.14623071462307The current socioeconomic and regulatory landscape of immune effector cell therapiesChiranjeevi Sainatham0Devvrat Yadav1Aravind Dilli Babu2Jayanth Reddy Tallapalli3Sai Gautham Kanagala4Evgenii Filippov5Franco Murillo Chavez6Nausheen Ahmed7Forat Lutfi8Department of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United StatesDepartment of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United StatesDepartment of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United StatesDivision of Infectious Diseases, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Internal Medicine, New York Medical College/Metropolitan Hospital Center, New York, NY, United StatesDepartment of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United StatesDepartment of Internal Medicine, Sinai Hospital of Baltimore, Baltimore, MD, United StatesDepartment of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, United StatesDepartment of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, United StatesImmune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell receptor (TCR) T cells, natural killer (NK) cells, and macrophage-based therapies, represent a transformative approach to cancer treatment, harnessing the immune system to target and eradicate malignant cells. CAR-T cell therapy, the most established among these, involves engineering T cells to express CARs specific to cancer cell antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, and multiple myeloma. Similarly, TCR-modified therapies, which reprogram T cells to recognize intracellular tumor antigens presented by major histocompatibility complex (MHC) molecules, offer promise for a range of solid tumors. NK-cell therapies leverage NK cells’ innate cytotoxicity, providing an allogeneic approach that avoids some of the immune-related complications associated with T-cell-based therapies. Macrophage-based therapies, still in early stages of the development, focus on reprogramming macrophages to stimulate an immune response against cancer cells in the tumor microenvironment. Despite their promise, socioeconomic and regulatory challenges hinder the accessibility and scalability of immune cell effector therapies. These treatments are costly, with CAR-T therapies currently exceeding $400,000 per patient, creating significant disparities in access based on socioeconomic status and geographic location. The high manufacturing costs stem from the personalized, labor-intensive processes of harvesting, modifying, and expanding patients’ cells. Moreover, complex logistics for manufacturing and delivering these therapies limit their reach, particularly in low-resource settings. Regulatory pathways further complicate the landscape. In the United States., the Food and Drug Administrations’ (FDA) accelerated approval processes for cell-based therapies facilitate innovation but do not address cost-related barriers. In Europe, the European Medicines Agency (EMA) offers adaptive pathways, yet decentralized reimbursement systems create uneven access across member states. Additionally, differing regulatory standards for manufacturing and quality control worldwide pose hurdles for global harmonization and access. To expand the reach of immune effector cell therapies, a multipronged approach is needed—streamlined regulatory frameworks, policies to reduce treatment costs, and international collaborations to standardize manufacturing. Addressing these socioeconomic and regulatory obstacles is essential to make these life-saving therapies accessible to a broader patient population worldwide. We present a literature review on the current landscape of immune effector cell therapies and barriers of access to currently approved standard of care therapy at various levels.https://www.frontiersin.org/articles/10.3389/fmed.2024.1462307/fullCAR T-cell therapyimmune effector cell therapyregulatory environment for cellular therapeuticsbispecific antibodies (BsAbs)TILs (tumor infiltrating lymphocytes)
spellingShingle Chiranjeevi Sainatham
Devvrat Yadav
Aravind Dilli Babu
Jayanth Reddy Tallapalli
Sai Gautham Kanagala
Evgenii Filippov
Franco Murillo Chavez
Nausheen Ahmed
Forat Lutfi
The current socioeconomic and regulatory landscape of immune effector cell therapies
Frontiers in Medicine
CAR T-cell therapy
immune effector cell therapy
regulatory environment for cellular therapeutics
bispecific antibodies (BsAbs)
TILs (tumor infiltrating lymphocytes)
title The current socioeconomic and regulatory landscape of immune effector cell therapies
title_full The current socioeconomic and regulatory landscape of immune effector cell therapies
title_fullStr The current socioeconomic and regulatory landscape of immune effector cell therapies
title_full_unstemmed The current socioeconomic and regulatory landscape of immune effector cell therapies
title_short The current socioeconomic and regulatory landscape of immune effector cell therapies
title_sort current socioeconomic and regulatory landscape of immune effector cell therapies
topic CAR T-cell therapy
immune effector cell therapy
regulatory environment for cellular therapeutics
bispecific antibodies (BsAbs)
TILs (tumor infiltrating lymphocytes)
url https://www.frontiersin.org/articles/10.3389/fmed.2024.1462307/full
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