Indapta Therapeutics: Advancing NK Cell Therapy for Cancer

Natural killer (NK) cells play a key role in detecting and eliminating cancerous or infected cells. Unlike T cells, they do not require prior sensitization, making them an attractive option for cancer immunotherapy. However, optimizing NK cell therapies to improve persistence, targeting, and scalability remains a challenge.

Indapta Therapeutics is developing enhanced NK cell treatments to address these limitations. By refining sourcing methods, employing genetic modifications, and improving expansion techniques, the company aims to create more effective and accessible therapies for cancer patients.

NK Cell Biology Concepts

NK cells are a subset of lymphocytes that serve as a first-line defense against malignant and virally infected cells. Unlike adaptive immune cells, they do not rely on antigen-specific receptors. Instead, they use a balance of activating and inhibitory receptors to determine whether to eliminate a target cell.

Their cytotoxic activity operates through two primary mechanisms: direct lysis via perforin and granzymes, and antibody-dependent cellular cytotoxicity (ADCC). In direct lysis, NK cells release perforin, forming pores in the target cell membrane, allowing granzymes to trigger apoptosis. In ADCC, NK cells express CD16 (FcγRIII), which binds to antibodies coating a target cell, leading to its destruction. The efficiency of these mechanisms depends on activating receptors such as NKG2D, NKp30, and NKp46, as well as inhibitory receptors like killer-cell immunoglobulin-like receptors (KIRs) and NKG2A.

Beyond their cytotoxic functions, NK cells regulate immune responses by secreting cytokines like interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which activate other immune cells. However, the tumor microenvironment can suppress NK function through inhibitory ligands, immunosuppressive cytokines like TGF-β, and metabolic alterations that reduce NK cell persistence. Overcoming these suppressive factors is critical for effective NK cell therapies.

Indapta’s Approach To NK Cell Sourcing

Developing effective NK cell therapies requires a scalable source of highly functional cells. Indapta Therapeutics has optimized NK cell sourcing to ensure consistency. Autologous approaches rely on patient-derived cells, but Indapta uses allogeneic NK cells, which allow for greater scalability and eliminate the need for individualized collection.

A key aspect of Indapta’s strategy is selecting NK cells from healthy donors with favorable immunogenetic profiles. The company prioritizes donors with high-affinity variants of CD16, which enhances ADCC. Individuals with the V/V genotype for the CD16 158 polymorphism exhibit stronger NK cell responses, improving therapeutic potency.

Indapta employs rigorous screening to identify NK cells with optimal functional characteristics, assessing activating receptor expression and functional assays measuring degranulation and cytokine secretion. These quality control measures standardize NK cell function across batches, ensuring consistent treatment efficacy.

Another innovation in Indapta’s sourcing strategy is the use of cytokine-induced memory-like (CIML) NK cells. Pre-activation with cytokines such as IL-12, IL-15, and IL-18 enhances NK persistence and cytotoxicity. CIML NK cells respond more effectively to tumor cells, improving durability and responsiveness in therapy.

Genetic Editing For Enhanced Tumor Targeting

Enhancing NK cell efficacy requires precise genetic modifications to improve tumor recognition and elimination. Indapta Therapeutics employs gene editing to optimize NK function and counter tumor-associated evasion mechanisms.

One strategy involves modifying NK cell receptors to improve tumor recognition. Knocking out inhibitory receptors like NKG2A or certain KIRs prevents tumors from exploiting inhibitory pathways that weaken NK activation.

Genetic engineering also enhances NK cell persistence and metabolic fitness. Tumor environments impose metabolic constraints by depleting nutrients and increasing oxidative stress. Indapta introduces modifications that improve mitochondrial function and glucose uptake, ensuring NK cells maintain cytotoxic potential in hostile conditions.

Another key aspect of Indapta’s approach is optimizing ADCC. High-affinity CD16 variants strengthen interactions with therapeutic monoclonal antibodies, improving tumor cell lysis. Stabilizing CD16 prevents its cleavage upon activation, ensuring sustained engagement with antibody-coated tumor cells.

Methods Of In Vitro Cell Expansion

Scaling NK cell therapies requires efficient in vitro expansion methods that preserve viability and functionality. Indapta Therapeutics has developed a refined expansion process to generate large quantities of potent NK cells while maintaining cytotoxic capabilities.

Optimized culture conditions support NK cell proliferation without inducing exhaustion or senescence. Carefully selected cytokine combinations promote sustained growth while preserving targeting ability.

Feeder cell systems provide crucial stimulatory signals. Indapta utilizes genetically engineered feeder cells expressing membrane-bound cytokines like IL-21 and co-stimulatory ligands such as 4-1BBL. These feeder cells enhance NK expansion rates while maintaining a favorable phenotype. Studies show that NK cells expanded with IL-21-expressing feeder cells develop a memory-like phenotype, improving persistence and responsiveness to tumor cells.