Cancer

Cancer poses a serious threat to human health due to its persistently high incidence and mortality rates. According to global cancer data released by the International Agency for Research on Cancer (IARC) of the World Health Organization, nearly 10 million cancer-related deaths were recorded worldwide in 2020.
Tumors are characterized by the unregulated division, growth, and spread of abnormal cells within the body, driven by complex interactions among genetic, epigenetic, and microenvironmental factors. Cancer remains a formidable challenge in the field of healthcare, as the rapid proliferation of abnormal cells can often bypass the body’s defense mechanisms and evade the immune system.

Immunotherapy

Immunotherapy encompasses treatment methods that leverage and enhance the immune system's ability to detect and destroy tumors, with the objective of achieving optimal therapeutic outcomes. Unlike conventional treatments which predominantly target tumor tissues, immunotherapy offers advantages such as enhanced specificity, broader applicability, and reduced incidence of adverse effects for patients. In recent years, driven by advances in cancer immunology and breakthroughs in molecular biology, immunotherapy has grown rapidly, surpassing traditional treatments such as surgery, chemotherapy, and radiation therapy to become the mainstream approach in cancer care. This paradigm shift has paved the way for innovative strategies, with tumor neoantigen immunotherapy emerging as a notable development.

Neoantigen

The paradigm shift in cancer treatment has sparked the exploration of innovative therapeutic strategies, with tumor neoantigen immunotherapy emerging as a prominent approach. At the core of this therapeutic paradigm is the concept of tumor neoantigens—unique, patient-specific antigens derived from somatic mutations within tumors.
A primary contributor of tumorigenesis is the accumulation of a substantial number of genetic mutations. As tumors progress, this genetic instability inevitably leads to the generation of a myriad of neoantigens. Under normal physiological conditions, the human immune system is proficient at identifying and eliminating these neoantigens that deviate from the body's self-antigens. This capability is integral to the immune system's vigilant surveillance and tumor-suppression function. However, in individuals with cancer, as tumor cells accumulate additional mutations, immune evasion becomes a prominent issue. The immune system's ability to fulfill this role becomes compromised, necessitating artificial intervention and enhancement. Given that neoantigens are uniquely expressed by cancer cells, they serve as ideal targets for the immune system to engage without causing harm to normal, healthy cells.
The pursuit of a vaccine to bolster the immune system’s capacity to detect and eradicate cancer has been a longstanding goal in oncology. Currently, an abundance of research has substantiated that tumor vaccines formulated with neoantigens can activate the body's inherent anti-tumor immune response, offering promising prospects for their application in cancer treatment.

Selection of Neoantigens

A critical step in the development of personalized tumor immunotherapy involves the identification of candidate neoantigens that can selectively trigger the body's immune response. Recent advancements in high-throughput sequencing technology, whole-genome and exome sequencing have enabled researchers to obtain comprehensive mutation data, including point mutations and insertions/deletions. The process involves initially obtaining tumor tissue from the patient, followed by high-throughput sequencing to preliminarily identify tumor cell mutation sequences, and subsequently employing AI algorithms for the prediction of potential tumor neoantigens. This complex process considers various factors, including HLA typing, TCR binding capacity, MHC affinity, and the origin of tumor neoantigens. 
Notably, Jinwei utilizes next-generation In-silico Neoantigen Identification Methods, which facilitates the rapid and precise identification of candidate neoantigens from experimental data and the selection of high-immunogenicity neoantigens.

Cryptic Peptide for Tumor Neoantigen Immunotherapy

Broad-Spectrum Tumor Neoantigen Targeting - Jinwei’s cryptic peptide technology is optimized through advanced big data modeling and experimental validation, enabling the modification of peptide sequences specifically designed for a wide range of tumors that express human Telomerase Reverse Transcriptase (hTERT). This includes "cold" or non-immunogenic tumors, which typically evade immune detection. This technology holds significant potential for broad clinical application by making these difficult-to-treat tumors accessible to immunotherapy.
Efficient Activation of Tumor-Infiltrating Lymphocytes - By enhancing the efficiency of antigen presentation, our cryptic peptides effectively stimulate the somatic immune system. This leads to the activation of Tumor-Infiltrating Lymphocytes (TILs), critical immune cells responsible for recognizing and attacking cancer cells. As a result, the technology promotes the eradication of tumor cells by driving a more powerful and targeted immune response.
Eliminating the Immune Desert - One of the key strengths of this approach lies in its ability to disrupt the hostile microenvironment of cold or non-immunogenic tumors. By activating CD8+ T cells and improving immune activation in these "immune deserts," the technology revitalizes the immune system’s ability to target and destroy tumor cells that were previously shielded from immune detection.
Potential as a PD-1 Equivalent in Clinical Applications - Our cryptic peptide technology breaks through immune tolerance mechanisms that typically limit the effectiveness of cancer treatments. By introducing a range of immune-activating factors that are often deficient in tumor microenvironments, it enhances immune responses within tumors. This approach complements the action of PD-1 inhibitors or antibodies, offering potential as a standalone or synergistic treatment, with comparable efficacy to PD-1 therapies in clinical settings.

Lentiviral Vector for Tumor Neoantigen Immunotherapy

Lentiviral vectors have also emerged as an indispensable tool in tumor neoantigen immunotherapy, demonstrating significant advantages in terms of transduction efficiency, sustained antigen expression, and customizable gene modification.
Efficient Gene Delivery - Lentiviral vectors pose the capacity to efficiently transduce both dividing and non-dividing cells, including Dendritic Cells (DCs) and Antigen-Presenting Cells (APCs). This capability is essential for the genetic modification of these cells to express neoantigens or to augment their antigen-presentation capabilities, which is crucial for initiating a robust immune response.
Sustained Expression - One of the hallmarks features of lentiviral vectors is their ability to mediate long-lasting transgene expression, enabling sustained neoantigen presentation to immune cells. This extended expression profile supports a more durable and effective immune response against tumor cells.
Customization - Lentiviral vectors can be precisely engineered to incorporate specific coding sequences for tumor neoantigens, allowing for personalized modifications that enhance the specificity and efficacy of immunotherapy.
Safety and Clinical Translation - Lentiviral vectors have been extensively studied in both preclinical and clinical settings for gene therapy applications, providing a well-established safety profile. This extensive background facilitates their translation into clinical use for neoantigen-based immunotherapies.
The application of lentiviral vectors in tumor neoantigen immunotherapy represents a promising frontier in cancer treatment. By harnessing the immune system's power to target the unique genetic mutations present in each patient’s tumor, lentiviral-based approaches could revolutionize cancer therapy, leading to more personalized and effective treatments.