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Neoantigen-based Immunotherapy Revolutionizes Cancer Treatment

Cancer immunotherapy is a rapidly advancing field in oncology that treats cancer by activating the immune system ^[1,2]. In recent decades, immunotherapy has shown significant efficacy and is considered a breakthrough therapy ^[1,2]. Tumor neoantigens, which are highly expressed in tumor cells and have strong immunogenicity, represent a promising new approach for cancer treatment ^[2]. Vaccines developed to target neoantigens have been tested in clinical trials for various cancers ^[3], including non-small cell lung cancer ^[4], pancreatic cancer ^[5], melanoma ^[6], colorectal cancer ^[7], and breast cancer ^[8], etc. The clinical trials of the neoantigen tumor vaccine are constantly increasing, and as of August 2024, through the clinical trial database. From January 1^st, 2015 to October 31^st, 2024, searching for clinical trials related to neoantigen tumor vaccines and tumors, it was found that the total number of projects has reached 133, of which 14 have been completed, 57 are still under recruitment ^[9].

Innovations in Neoantigen Peptide Process Development

Neoantigens are categorized into two types: shared neoantigens and personalized neoantigens ^[2,10]. Shared neoantigens are mutated antigens that are common across different cancer patients but absent in the normal genome ^[2]. In contrast, personalized neoantigens are unique to individual patients, differing from one another and generally not shared across cases ^[2,11]. Challenges faced by neoantigen peptides production include high hydrophobicity, low coupling efficiency, difficult purification and other production issues. Moreover, when applied to personalized therapy, the overall production cycle is short and rapid production is required to ensure timely delivery. Equipment like the CEM fully automatic microwave synthesizer can be employed to expedite peptide synthesis, opening up new synthesis pathways. Process development techniques can then be applied to address the challenges associated with neoantigen peptide production. The specific process developments are as follows:

1）Synthesis Process Development

2） Cleavage and Precipitation Process Development

3） Purification and Salt Exchange Process Development

4）Lyophilization Process Development

Quality Control and Assurance

In the cGMP quality system, the five elements constitute the foundation for ensuring drug quality and safety. The cGMP factory is designed and constructed based on the cGMP requirements of major regulatory agencies such as the US FDA, EMA, PMDA, and the National Medical Products Administration. GenScript has established a cGMP quality management system, covering raw materials, facilities and equipment, laboratory control, production, packaging, and labeling. Due to the special physical and chemical properties of neoantigen peptide, sterile preparations generally do not use the production process of hot-pressure sterilization of the final product. In most cases, the aseptic production process of filtration sterilization is used. Because bacteria can degrade peptides, resulting in a decrease in peptide purity, sterile conditions can allow peptides to be stored for longer periods of time, thereby ensuring the purity, stability, and activity of peptides. GenScript is fully equipped with sterile assurance capabilities, ensuring product sterility through systematic and stringent controls.

Accelerate Customer Research in Tumor Immunotherapy

On October 9^th, 2024, Beijing Zhenzhi Medical Technology Co., Ltd. (referred to as "Zhenzhi Medical"), which focuses on the development of solid tumor immune cell therapy, mRNA tumor therapeutic vaccines, and TCR drugs, announced that its independently developed and produced IPM001 injection new drug Phase I clinical research application (Investigational New Drug, IND) has been granted implied permission by the National Medical Products Administration (NMPA).

GenScript, as the supplier of neoantigen peptides in this project, synthesized specific neoantigen peptides, contributing to the development and validation process of IPM001 injection.

With rich experience in peptide synthesis, GenScript offers a one-stop solution for neoantigen peptide services, covering the entire neoantigen peptide research lifecycle—from early-stage screening and research-grade synthesis to preclinical studies and clinical trials.

The GenScript RUO(Research Grade) manufacturing facility utilizes multiple technology platforms built on years of big data accumulation, from peptide property prediction to peptide synthesis and process optimization. Research-level delivery time is as fast as 5 days, while clinical-level delivery time can be as quick as one week, with a success rate exceeding 98%.

The GenScript cGMP manufacturing facility can deliver up to 48 neoantigen sequences per patient per batch (up to 500 per month), along with sterilization filtration and sterile filling services. The dedicated GMP production line includes a Grade A isolator for sterile filtration and highly customized aseptic processing for human injection projects.

Interested in learning more about our neoantigen peptide synthesis capabilities, please contact us at [email protected].

References

[1] Schumacher T N, Schreiber R D. Neoantigens in cancer immunotherapy[J]. Science, 2015, 348(6230): 69-74.

[2] Zhang Z, Lu M, Qin Y, et al. Neoantigen: A new breakthrough in tumor immunotherapy[J]. Frontiers in Immunology, 2021, 12: 672356.

[3] Rappaport A R, Kyi C, Lane M, et al. A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results[J]. Nature Medicine, 2024, 30(4): 1013-1022.

[4] Awad M M, Govindan R, Balogh K N, et al. Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer[J]. Cancer Cell, 2022, 40(9): 1010-1026.

[5] Rojas L A, Sethna Z, Soares K C, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer[J]. Nature, 2023, 618(7963): 144-150.

[6] Ott P A, Hu Z, Keskin D B, et al. An immunogenic personal neoantigen vaccine for patients with melanoma[J]. Nature, 2017, 547(7662): 217-221.

[7] Yu Y, Zhang J, Ni L, et al. Neoantigen-reactive T cells exhibit effective anti-tumor activity against colorectal cancer[J]. Human Vaccines & Immunotherapeutics, 2022, 18(1): 1-11.

[8] Blass E, Ott P A. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines[J]. Nature reviews Clinical oncology, 2021, 18(4): 215-229.

[9] https://clinicaltrials.gov/

[10] Katsikis P D, Ishii K J, Schliehe C. Challenges in developing personalized neoantigen cancer vaccines[J]. Nature Reviews Immunology, 2024, 24(3): 213-227.

[11] Xie N, Shen G, Gao W, et al. Neoantigens: promising targets for cancer therapy[J]. Signal transduction and targeted therapy, 2023, 8(1): 446-483.