GeneBio Therapeutics Announces First Complete Response in Relapsed/Refractory B-NHL Patient Treated with In Vivo CAR-T Therapy

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Shenzhen Jiinno Biotechnology Co., Ltd. ("Jiinno Biotech" for short) independently developed an in vivo CAR-T cell therapy targeting CD19 (In Vivo CAR-T), which has launched an Investigator-Initiated Trial (IIT) at the Biological Cell Treatment Center of the First Affiliated Hospital of Zhengzhou University. Recently, this clinical trial achieved a breakthrough: a subject with a high tumor burden suffering from relapsed/refractory diffuse large B-cell lymphoma (a type of B-cell non-Hodgkin lymphoma) received the in vivo CAR-T cell therapy and achieved complete remission (CR) before being discharged. During the in vivo CAR-T treatment process, the patient remained stable, achieved complete remission (CR) one month after administration, and did not experience common CAR-T treatment side effects such as grade 2 or higher cytokine release syndrome (CRS) or neurotoxicity (ICANS).

In recent years, the in vivo CAR-T technology has emerged as a standout in the biopharmaceutical field, becoming a focal point of the industry. Although traditional CAR-T technology has achieved remarkable success in cellular immunotherapy, it also faces some challenges, such as complex cell collection, preparation, and reinfusion processes, high production costs, and long treatment waiting times, which severely affect its commercial accessibility. In vivo CAR-T technology appears as a revolutionary approach; it does not require the extraction of patients' immune cells for ex vivo modification. Instead, it uses specific targeted vectors to precisely deliver CAR molecules to T cells within the patient’s body, directly editing the T cells in vivo to generate autologous CAR-T cells with strong activity and expansion capabilities. This will greatly simplify the cell preparation process, reduce production costs, and can be used as an off-the-shelf product, shortening patient waiting time.

In terms of treatment efficacy, the in vivo CAR-T technology demonstrates excellent performance in precisely targeting and eliminating tumor cells, even when using autologous T cells. By delivering modified genes directly to T cells in the body via a special vector, the T cells are transformed into CAR-T cells with potent anti-cancer capabilities. These CAR-T cells act like precision-guided missiles, specifically identifying cancer cells and launching attacks, offering cancer patients more hope for survival.

In addition, the in vivo CAR-T technology also provides possible solutions for the treatment of more types of cancer. Currently, it has shown potential in the treatment of hematologic malignancies, and in the future, it may be expanded to other cancer fields such as autoimmune diseases and solid tumors. Many research teams and companies in the industry have invested in the research and exploration of in vivo CAR-T technology, which undoubtedly leads the entire biopharmaceutical industry towards a more efficient and precise direction for cancer treatment.

Notably, on July 10, 2024, Interius BioTherapeutics announced that it had received clinical trial approval from the Therapeutic Goods Administration (TGA) in Australia to conduct a Phase 1 clinical trial of its investigational in vivo CAR-T therapy, INT2104, for the treatment of B-cell malignancies. At that time, industry reports indicated that INT2104 was the first in vivo CAR-T therapy to enter human clinical trials. Subsequently, on August 1, 2024, Umoja Biopharma announced that its investigational CD19-targeted in-situ generated CAR-T cell therapy, UB-VV111, had received FDA IND approval for the treatment of hematologic malignancies. These developments highlight the rapid advancement and promising application prospects of the in vivo CAR-T field on a global scale.

B-cell Non-Hodgkin Lymphoma (B-NHL) is a malignant tumor originating from B lymphocytes, accounting for a significant proportion of Non-Hodgkin Lymphoma (NHL). From the etiological perspective, its occurrence is related to various factors. Infectious factors cannot be ignored; for example, Epstein-Barr virus (EBV) infection is associated with certain types of B-NHL, such as Burkitt lymphoma, which is closely related to EBV infection. The risk of developing B-NHL is also significantly increased in patients infected with Human Immunodeficiency Virus (HIV), possibly due to HIV-induced immune dysfunction, leading to reduced surveillance and suppression of B-cell malignancies by the body. Additionally, immune factors play an important role in the pathogenesis of B-NHL. Patients with autoimmune diseases who have been using immunosuppressants for a long time or those receiving immunosuppressive therapy after organ transplantation have a relatively higher incidence of B-NHL because, under immunosuppressive conditions, B cells are more prone to abnormal proliferation and malignancy.

B-NHL is highly heterogeneous with diverse pathological types and varying clinical manifestations. Patients may experience painless lymphadenopathy, the most common symptom, with enlarged lymph nodes appearing in areas such as the neck, armpits, or groin. As the disease progresses, it may involve organs like the bone marrow, liver, and spleen, leading to complications such as anemia, thrombocytopenia, and hepatic dysfunction. Patients often suffer systemic symptoms including fever, night sweats, and weight loss, which not only affect their quality of life but also pose a severe threat to their survival as the disease advances.

In recent years, CAR-T therapy has achieved significant breakthroughs in the treatment of B-NHL, bringing new hope to patients. In China, there are already CAR-T products approved for marketing as cellular therapeutic agents, used to treat adult patients with relapsed or refractory large B-cell lymphoma who have received two or more lines of prior systemic therapy. Their price is approximately 1.2 million yuan, offering a new treatment option for many relapsed or refractory patients.

Similarly based on the principle of CAR-T cell therapy, the innovative in vivo CAR-T therapy greatly simplifies the manufacturing process and treatment procedure, significantly reducing treatment costs. With no waiting time and the drug readily available, it truly holds the potential to realize the promising vision of curing cancer with a single injection, without imposing excessively high manufacturing costs on patients.

Jiyin Bio's recently disclosed clinical data marks the first publication of clinical results for in vivo CAR-T therapy. Preliminary data shows that in vivo CAR-T therapy has demonstrated good safety and efficacy. This treatment is based on Jiyin Bio’s proprietary VivoExpress technology platform, utilizing lentiviral delivery technology to achieve the production of CAR-T cells in vivo. It exhibits strong targeting ability and T-cell infectivity, and can effectively kill cancer cells.

Jiyin Bio stated: "We are very excited to witness the outstanding performance of our in vivo CAR-T therapy in clinical trials. This is not only an affirmation of our team's relentless efforts, but also brings new hope to a wide range of cancer patients. We will continue to push forward with the clinical development process of the product, striving to bring it to market as soon as possible, providing more patients with effective treatment options."

Source: JiYin Biotechnology