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By killing cancer cells directly within the tumor, the treatment exposes the patient's unique, mutated cancer antigens to their immune system. This effectively trains immune cells to recognize and attack similar cancer cells throughout the body, creating a highly personalized, in-situ vaccine.
Previous cancer vaccine attempts using "shared antigens" failed. Moderna's success stems from creating a unique mRNA vaccine for each patient after discovering that roughly 90% of the targeted cancer antigens differ between individuals. This finding proves that a highly personalized approach is not just an edge case, but a core requirement for the therapy's efficacy.
The company's technology is a delivery system. By containing potent compounds within the tumor via direct injection, it can make previously shelved drugs—those too toxic for systemic use—viable therapies, creating a new pipeline of cancer treatments.
The key rationale for neoadjuvant immunotherapy is that an in-situ tumor provides a rich source of antigens. Treatment primes the immune system against these targets, creating a powerful, systemic immunological memory that can effectively eliminate micrometastatic disease before and after surgery.
The drug exhibits a multimodal mechanism. It not only reverses chemoresistance and halts tumor growth but also 'turns cold tumors hot' by forcing cancer cells to display markers that make them visible to the immune system. This dual action of direct attack and immune activation creates a powerful synergistic effect.
Injecting a genetic medicine into one tumor can trigger an 'abscopal response,' where the immune system learns to recognize the cancer. This educated immune system then travels throughout the body to find and destroy other metastatic tumors, even those in deep organs like the lungs, which are typically the fatal ones.
By delivering a high, sustained local drug concentration, Nenology's platform shifts cancer cell death from a passive process (apoptosis) to immunogenic cell death. This releases antigens that actively prime the immune system, creating a secondary anti-tumor effect and potentially boosting the efficacy of other immunotherapies.
While personalized cancer vaccines require extracting and processing a patient's tumor, Create Medicines' in vivo approach is entirely off-the-shelf. By delivering the programming directly into the body, they enable the patient's own immune system to do the complex, personalized work of attacking the cancer itself.
The company's drug formulation doesn't rely on specific cell receptors, which cancers often mutate to evade treatment. Instead, it uses a physical diffusion process to permeate any cancer cell, rendering receptor-based mutations irrelevant and overcoming a major hurdle in cancer therapy.
Administering immunotherapy while the primary tumor and lymph nodes are intact allows them to act as an "in-situ vaccine." This generates a more diverse and powerful systemic immune response against cancer cells throughout the body compared to treating after surgical removal of these antigenic sources.
An emerging area of research is intralesional immunotherapy, where anti-PD-1 drugs are injected directly into early-stage cutaneous squamous cell carcinomas. This approach may provide effective local control for tumors in anatomically challenging locations while minimizing systemic toxicity.