On June 28, 2021 ImmunityBio, Inc., a publicly traded immunotherapy company, and privately-held NantOmics reported publication of a stepwise approach or "pipeline" for identification and validation of neoepitope and neoepitope-reactive T cells from individual patients (Press release, ImmunityBio, JUN 28, 2021, View Source [SID1234584402]). The identification of neoepitopes—short peptide sequences that are mutated in tumors and are capable of generating an immune response—provides critical support in the successful development of next-generation immunotherapies delivered by ImmunityBio’s Adeno- and yeast-based platforms. The pipeline is described in "Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy," which recently published in the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).
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The pipeline leverages the bioinformatics capabilities of NantOmics and ImmunityBio to predict neoepitopes based on genomic and expression analyses that have a high likelihood of generating a tumor-fighting immune response and the generation of neoepitope-specific CD4+ and CD8+ T cells when delivered using the Adeno and yeast vaccine platforms. These predicted neoepitopes once identified are synthesized as short peptides, and run through a series of studies to confirm their potential utility in the cancer vaccine platforms. The pipeline was developed in conjunction with physicians and scientists at Friedrich Alexander University in Germany and the National Cancer Institute (NCI) in the U.S.
In clinical use, this neoepitope discovery system supports the targeted delivery of antigens with ImmunityBio’s second-generation Adeno platform. This platform, which has shown promising results in Phase 1 and 2 trials, activates CD4+ and CD8+ T cells after delivery of tumor-associated antigens in patients with advanced solid tumors and colon cancer. In preclinical studies conducted in collaboration with the NCI, accurate prediction of neoepitopes, delivered via the adenovirus platform, resulted in complete response in colon cancer when combined with ImmunityBio’s IL-15 superagonist Anktiva and other immune-based therapies. That study highlights the potential for neoepitope identification to inform highly effective anti-tumor therapy.
"The future of immunotherapy is in a personalized approach," said Dr. Patrick Soon-Shiong, Founder and Executive Chairman of ImmunityBio. "By tailoring therapies to the individual biology of each patient’s cancer, we greatly increase the likelihood of successful treatment using our ever-increasing arsenal of immune-based therapies."
"Validation of the neoepitope identification pipeline in actual patients from the TILGen study was an important aspect of the proposed method," said Dr. Peter Fasching, who with Dr. Anita Kremer, was senior author on the manuscript. "We were able to isolate the specific immune cells that recognized the predicted neoepitopes. Those immune cells aimed at the cancer cells’ neoepitopes are very important because they could potentially kill a tumor. Clinically, the predicted and confirmed neoepitopes could be targeted by vaccines or adoptive cell transfer therapies and improve patient outcomes."
Neoepitopes can be unique for each patient and when the pipeline is applied, the analyses for identification of these neoepitopes would be performed using tumor and other tissues collected from individual patients.
This method for identifying tumor-specific immunogenic targets for individualized treatment can be used as part of a program including other immune and cell-based therapies available through ImmunityBio, including CAR T-cell therapies and vaccines. Efficacy of these therapies could be further enhanced by combination with an immune enhancer such as ImmunityBio’s Anktiva or Natural Killer (NK) cells.
About the Neoepitope Identification Pipeline
The bioinformatics methodology, well-established at NantOmics, readily and accurately predicts neoantigens;
Practical cell-based assays of synthesized neoepitope peptides refines candidates to those most likely to induce an immune response;
and Tissues and cells routinely collected from individual cancer patients can be used to confirm and further narrow neoepitope candidates.
The neoepitope identification and validation pipeline is feasible, practical and accurate, as this first report suggests. It is anticipated that it will be applied in future clinical studies of immunotherapies to determine the merits of this personalized approach to precision medicine for cancer.