AdVince - Oncolytic virus in an ongoing phase I/II-study, sponsored by Uppsala University, for treatment of neuroendocrine tumors
Elicera's oncolytic virus AdVince (ELC-100) is based on a genetically modified adenovirus, Ad5PTD, that has been optimized with regards to its ability to selectively infiltrate and replicate in neuroendocrine cancer cells. When new virus particles have formed in enough numbers, tumor cells burst through a so-called immunogenic oncolysis, releasing factors that can also activate the immune system. When the tumor cell dies, an immune response to the cancer is also triggered by the release of neoantigens which are picked up by the patient's antigen-presenting dendritic cells, which then train T-cells in to attack cancer cells wherever they are in the body. In this way, AdVince is expected to achieve a local tumor-killing effect in the injected tumor while simultaneously triggering a long-term and systemic immune response through a T-cell attack on cancer cells in other parts of the body as well.
Next-generation oncolytic immunotherapy with three combined mechanisms of action.
Elicera's next-generation oncolytic immunotherapy, ELC-201, is based on a genetically modified adenovirus vector, with three combined mechanisms of action. The treatment is expected to work synergistically with established immune checkpoint inhibitors and can theoretically be used for the treatment of all injectable solid tumors.
In preclinical studies, ELC-301 has been shown to be able to induce an immune response that kills even those cancer cells that do not express the CAR T-cell antigen
In November 2019, the Swedish Cancer Society granted Professor Magnus Essand a total of SEK 13.5 million over three years to develop cancer immunotherapies, of which SEK 4.5 million for preclinical development of ELC-401 against brain tumors and SEK 9 million in preparation for clinical development of ELC-301, against difficult-to-treat Non-Hodgkin's B-cell lymphoma (NHL). In contrary to many other CAR T-cells that target CD19, ELC-301 targets the CD20-antigen which is expressed on virtually all NHL tumor cells.
Today, NHL is primarily treated with chemotherapy in combination with an anti-CD20 antibody called Rituximab. Over 50 percent of patients are cured but between 20-50 percent of these patients stop responding to standard treatment or relapse after complete response. It is these patients that ELC-301 initially targets.
Alternatively, the patients relapsing from chemotherapy and Rituximab can be treated with approved CD19 CAR T-cell therapy (Kymriah or Yescarta). However, only about 40 percent of patients with B-cell lymphoma who are treated with CD19 CAR T-cell therapies receive a sustained complete response. 30 percent of patients are resistant to CD19 CAR T-cell therapies and 20 percent relapse after CAR T-cell therapy. Elicera's iTANK-enhanced CD20-based CAR T-cell therapy, ELC-301, can be used also to treat non-responding or relapsing CD19 CAR T-cell therapy patients and thus has the potential to more than double the number of B-cell lymphoma patients with complete sustained tumor response.
Since NHL tumors can have an immunosuppressive tumor microenvironment and there is also a potential problem with therapeutic resistance because the cancer cells can lose the target antigen for CAR T-cell therapy, it is of utmost importance that next generation CAR T-cell treatments also are able to induce a powerful immune response based on neoantigen reactive CD8+ T-cells that can kill cancer cells that do not express the target antigen. ELC-301 has therefore been programmed with an immune stimulatory factor (NAP) via the iTANK platform, which in preclinical studies has been shown to be able to induce an immune response that also kills the cancer cells that do not express the CAR-target antigen.
Elicera Therapeutics has developed ELC-401, a new type of CAR T-cell therapy for the treatment of solid tumors, initially for glioblastoma. The CAR T-cells target IL-13Rα2 and have also been enhanced with the iTANK platform for a more powerful immune response via neoantigen-activated T-cells. IL-13Rα2 is overexpressed in about 75 percent of all glioblastomas, but also in a number of other solid tumors such as colon cancer, pancreatic cancer, ovarian cancer and melanoma.
The first step of the study has four dose levels with three patients at each level. In addition to looking at side effects, the patients are also examined for efficacy. A complete treatment consists of four injections over the course of about seven weeks. ELC-100 is injected using X-ray technology via blood vessels from the groin into the liver. The patient is evaluated one month later with combined advanced medical technology (CT, MRI, PET). At present, seven, out of a total of 12 planned patients have been treated.
Although it is too early to draw any conclusions from the study, data reported so far by Uppsala University show some promising signs of efficacy from one of the patients.