CAR-T Cell Therapy

CAR-T cell therapy in India requires a paradigm shift in training, education and health care processes

Akshay Ravindranath1 , Aparajita Dubey1 , Surekha Suresh3 , Guljit Chaudhuri2 , Narendra Chirmule1,

1 SymphonyTech Biologics, Philadelphia, PA
2 BioInnovat, New Delhi
3 Biofusion Therapeutics, Bangalore

ARTICLE INFO

Article History:
Received 11 May 2021
Accepted 13 September 2021
Available online xxx

Key words:
affordable medicine
cancer therapy
CAR-T cell therapy
challenges
GMP
India

ABSTRACT

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of some kinds of cancers.
Hundreds of companies and academic institutions are collaborating to develop gene-modified cell therapies
using novel targets, different cell types, and manufacturing processes of autologous and allogenic cell therapies. The individualized, custom-made autologous CAR-T cell production platform remains a significant limiting factor for its large-scale clinical application. In this respect, the advances in standardization and
automation of the process can have considerable impact on cost reduction. Development of off-the-shelf,
ready-to-use universal killer cells can enable scaling up. Despite the wide use of this cell therapy in the
United States, Europe and China, its development is limited in developing countries in Southeast Asia, Africa
and Latin America. In this review, we focus on good manufacturing practicescompliant manufacturing
requirements, operational logistics, and regulatory processes that need to be considered for high-quality
gene-modified cell therapies from an Indian perspective. We also list the potential strategies to overcome
challenges associated with translation to affordability and scalability.
© 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

Introduction

Immunotherapy is transforming the clinical outcomes of cancer
treatment. These outcomes were once considered unachievable. Cell
and gene therapy technologies are enabling the development of novel
products and regimens that have been successful in curing certain
types of cancers. In India, according to a projection by National Cancer
Registry, there were 1.39 million patients with cancer in the year
2020, whereas this number was 8 million worldwide [1]. Further, this
number is likely to increase 5-fold by 2025 [2,3]. The challenges with
cancer treatment in India involve lack of early diagnosis, misinformation about treatment, lack of knowledge of physicians and health care
providers, low trust in public health services, inadequate infrastructure
[36], and unfortunately, corruption within the health care system [7].
Because of these issues, 80% of health expenditure is diverted to the
private sector. Figure 1 shows the geographical distribution of leukemia cases and bone marrow transplantation centers in India. The standard of care for the various types of cancers include surgery, radiation,
chemotherapy and immunotherapy. In 2019, the National Cancer Grid
[8], a consortium of cancer care centers, released guidelines for Indian
patients to standardize cancer care across the country. The National Health Authority (NHA) of India has covered most poor patients for
cancer care through their public health insurance scheme [9]. Such
government initiatives are encouraging cancer research and expediting
the development of novel diagnostics and therapeutics in India.
The Indian pharmaceutical companies have been world leaders in
the manufacturing of generic medicines and vaccines [10,11]. The
availability of these generic medicines, which primarily comprise cytotoxic

 and cytostatic drugs, enables first-line treatment for most
patients with cancer. However, as most of these first-line therapies
result in relapse, second- and third-line therapies, which comprise biologic drugs, are required. These drugs are expensive for most patients
with cancer in India. Recently, the advent of biosimilars for highly
effective monoclonal antibodies such as trastuzumab, rituximab, and
bevacizumab has considerably improved the clinical outcomes of cancer treatment in India. Soon, biosimilars of ipilimumab and pembrolizumab are also likely to have significant impact on clinical outcomes.
However, despite the advancement of treatment regimens and
government-sponsored initiatives, there continue to be many challenges regarding access to treatment for the growing numbers of
patients with cancer in India, especially for middle- and low-income
groups. Globally, more than a hundred companies are developing cell
and gene therapies and related products, which are involved in >1,220 clinical trials, as of May 2021 [12].  In India, only four companies are currently initiating chimeric antigen receptor (CAR)-T
cell programs [13]: Immuneel Therapeutics (Bangalore), ImmunoACT
(Mumbai), Aurigene (Hyderabad) and Intas (Ahmedabad). The aim of
this article is to briefly review the current advances in cell and gene
therapies for cancer, define the challenges involved in providing access
to affordable first-line treatment to all patients with cancer in India,
and propose potential solutions for the same. These solutions are (i)
developing affordable infrastructure, which includes logistics, quality
and regulatory considerations for treatment; (ii) developing a training
and education system for providers of high-technology services; and
(iii) enabling discovery research for collaboration and innovation for
processes to improve the efficiency of cancer treatment regimens.

© 2020 Bioinnovat - All Rights Reserved.