Antibodies and Their Derivatives in Cancer Immunotherapy for Gastrointestinal Cancers

Dear Colleagues,

Monoclonal antibodies, developed via hybridoma technology, a technology that also helped Georges Köhler, César Milstein, and Niels Jerne to win the Nobel prize in Physiology or Medicine in 1984, played a significant role in controlling several disease types. Applying the product of this Nobel prize-winning work in their revolutionary effort on the application of immune checkpoint blocker (ICB) monoclonal antibodies to improve the anticancer capabilities of T cells, in 2018, James P. Allison and Tasuku Honjo won the Nobel prize in Physiology or Medicine.

Immune checkpoints, e.g., PD1-PDL1, CTLA-4-CD80/86, TIGIT-CD155, and NKp44-PCNA, play a significant role in suppressing the cytotoxic function of T cells as well as NK cells in the tumor microenvironment. Immune checkpoint blocker (ICB) monoclonal antibodies can block these receptor–ligand integrations and, thus, can release the immune suppression. Immune checkpoint blocking immunotherapies showed tremendous success in the clinic for different cancer types. For this paradigm shift in cancer treatment, the US FDA approved several immune checkpoint blocking monoclonal antibodies like Ipilimumab, Nivolumab, Pembrolizumab, Atezolizumab, Durvalumab, Relatlimab, etc., for the treatment of different cancer types.

Despite being successful in treating several cancer types, the success is very limited in gastrointestinal cancers, like in pancreatic cancer, where immune checkpoint blocking antibodies showed no such success. Similarly, for colorectal cancer, ICB treatment efficacy is limited for the microsatellite stable group. In most scenarios where ICB treatment works for a while, treatment resistance is another hurdle.

Following the success of ICB, Chimeric Antigen Receptor (derived from ScFv of monoclonal antibodies) expressing T cells (CAR-T cells) targeting tumor-specific antigens like CD19 for B cell malignancy, BCMA for multiple myeloma showed tremendous success in the clinic for the hematological malignancy. The US FDA approved CAR-T cell therapy, e.g., ABECMA, BREYANZI, CARVYKTI.

But for solid tumors, the success rate is negligible. None of the approved CAR-T cell therapies has shown success for gastrointestinal cancers.

In the current scenario, it is very important to understand the mechanism behind the treatment failure of the ICB as well as CAR-T cells in gastrointestinal cancers. How we can improve their cytotoxic function is also important.

We are pleased to invite you to contribute to this Special Issue named “Antibodies and their Derivatives in Cancer Immunotherapy for Gastrointestinal Cancers” to strengthen our understanding of the application of antibodies and their derivatives to improve cancer immunotherapy in this cancer group.

The aim of the Special Issue is to present original research articles as well as review articles presenting novel findings on monoclonal antibodies and their derivatives-based cancer immunotherapy, and molecular mechanisms explaining the reason behind immunotherapy failure in different gastrointestinal cancer types.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

• Characterizations of novel immune checkpoints associated with gastrointestinal cancer types;
• Modulation of immune checkpoints using monoclonal antibodies;
• Monoclonal antibody-derived CAR- immune cells for gastrointestinal cancer types;
• Monoclonal antibody-based T/NK cell engagers;
• Antibody drug conjugates;
• A rational novel combination of immune checkpoint blockers with another drug to improve immunotherapy in gastrointestinal cancer types.

We look forward to receiving your contributions.

Dr. Kiran Kundu
Dr. Susmita Ghosh
Guest Editors

Manuscript Submission Information

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• gastrointestinal cancer
• immunotherapy
• immune checkpoint blocker
• monoclonal antibody
• CAR
• bispecific antibody
• T cell engager
• NK cell engager