Indapta's IDP-023 Shows Promise in Multiple Myeloma and Enhanced NK Cell Activity
核心洞察
Indapta Therapeutics (搜索)' IDP-023 demonstrated preliminary clinical activity in relapsed/refractory multiple myeloma (搜索) patients, even at the lowest dose without a targeting antibody.
Phase 1 trial data showed objective responses in five of nine patients treated with IDP-023, with notable reductions in serum M-protein or light chain levels in myeloma patients.
Preclinical data highlights IDP-023's enhanced antibody-dependent cellular cytotoxicity (ADCC) driven by faster cell migration and increased immune synapse formation.
Indapta Therapeutics (搜索) presented clinical and preclinical data on its allogeneic natural killer (NK) cell therapy, IDP-023, at the Society for Immunotherapy of Cancer (SITC) meeting, showcasing promising results in multiple myeloma (搜索) and enhanced NK cell activity. The data suggest potential advancements in cancer treatment through differentiated cell therapies.
Clinical Activity in Multiple Myeloma
The clinical presentation (Abstract #1483) highlighted data from the safety run-in of a Phase 1/2 study, evaluating IDP-023 in patients with advanced multiple myeloma (搜索) or non-Hodgkin lymphoma (搜索). Patients received one to three doses of IDP-023, with or without interleukin-2 (IL-2). The treatment was generally well-tolerated, with the most common adverse events being cytopenias related to the conditioning chemotherapy. Encouragingly, objective responses were observed in five of nine patients. Specifically, four out of five patients treated with IDP-023 and IL-2 achieved an objective response, including one very good partial response, two partial responses, and one minimal response. In eight relapsed/refractory myeloma patients, the mean maximum decrease in serum M-protein or light chain was 73%, with three patients achieving a reduction of 84% or greater.
Dr. Robert Sikorski, Chief Medical Officer of Indapta, stated, "We are encouraged to observe this degree of clinical activity during the safety run-in, at the lowest cell dose and without the addition of a targeting antibody." The company anticipates further enrollment in antibody cohorts, combining IDP-023 with CD38 (搜索)-targeting monoclonal antibodies for multiple myeloma (搜索) and CD20 (搜索)-targeting monoclonal antibodies for non-Hodgkin’s lymphoma, based on preclinical models indicating markedly increased efficacy with the addition of a targeting monoclonal antibody.
Enhanced NK Cell Activity
Abstract #365 detailed how artificial intelligence-based dynamic single-cell imaging revealed enhanced migration and immune synapse formation by IDP-023. Researchers demonstrated that the enhanced antibody-dependent cellular cytotoxicity (ADCC) of g-NK cells is driven partly by faster cell migration and a higher frequency of synapse formation with target cells compared to conventional NK cells. Faster migration correlates with enhanced expression of CD2 (LFA-2), a protein involved in leukocyte adhesion, potentially contributing to the increased migration and cytotoxic functions of IDP-023.
Potent Activity Against Solid Tumors
In Abstract #1285, data demonstrated the potent activity of g-NK cells against HER2 (搜索) and EGFR (搜索) positive cell lines, both without and with tumor-targeting antibodies. Analysis of publicly available datasets of patients treated with trastuzumab, a monoclonal antibody used to treat HER2-positive breast and other cancers, showed that patients with increased levels of naturally occurring g-NK cells had a higher rate of pathological complete response in a neoadjuvant study and improved distant disease-free survival in an adjuvant study.
Stefanie Mandl-Cashman, Chief Scientific Officer of Indapta Therapeutics (搜索), commented, "These data demonstrate both the differentiated mechanism of g-NK cells, as well as their potential efficacy in solid tumors." She also highlighted the powerful effect of naturally occurring g-NK cells on the outcome of patients undergoing therapy with monoclonal antibodies, demonstrating the strong antibody-dependent cellular toxicity of g-NK cells.
About Indapta’s g-NK Cell Therapy
Indapta's allogeneic NK cell therapy platform utilizes a subset of naturally occurring NK cells, known as “g minus” NK cells, or “g-NK” cells, which arise from epigenetic changes resulting from exposure to cytomegalovirus (CMV). IDP-023 is generated by preferentially expanding g-NK cells from healthy donors, exhibiting low donor-to-donor variability. The therapy has multiple mechanisms of killing target cells without genetic engineering, including robust ADCC, targeting of HLA-E expressing cells via the NKG2C receptor, and inherent anti-viral activity.
Indapta’s g-NK cells can release significantly more immune-activating cytokines and cell-killing compounds than conventional NK cells. Preclinical studies have shown that IDP-023, combined with cancer-targeting monoclonal antibodies, demonstrates more potent and durable antitumor activity compared to conventional NK cells. g-NK cells, in combination with a B cell-targeting antibody, can also deplete normal B cells from healthy donors or patients with autoimmune disease.