CAR T-cell therapy for treatment of Non-Hodgkin's B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of cancer that originates in the B cells of the immune system. DLBCL is one of the world's most common B-cell cancers and the disease has a rapid progression, which requires treatment to be initiated as soon as possible after the diagnosis is established. ELC-301 is being developed for patients suffering from a particularly severe form of DLBCL or who suffer relapse after several rounds of standard treatment.
Today's standard treatment consists of a combination of chemotherapy and antibodies and 60-70% of patients are cured. In patients who suffer relapse, CAR T-cell therapy is the next step in the treatment ladder. Despite the fact that the disease disappears in many after CAR T-cell treatment, the relapse rate is high in the patient group – up to 50% – and treatment options in the form of more advanced therapies are limited.
Today's approved CAR T-cell therapies target the tumor target CD19 – a common B-cell protein that is overproduced on the surface of cancer cells in DLBCL. In many of the individuals who suffer from relapse, this tumor target disappears and further treatments with the same CAR T therapy therefore become ineffective. ELC-301 instead targets CD20, which is also overrepresented in B-cell lymphoma. By switching targets to CD20, ELC-301 enables the treatment of relapsed patients who are in need of a new effective alternative.
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.
The company hs an ongoing clinical phase I/IIa trial called CARMA with ELC-301 in a total of 18 cancer patients. The trial will be conducted in two stages, a dose escalation study and a dose optimization study. The first sub-study is conducted in three cohorts – of three, three and six patients – and aims to find the maximum tolerated dose (MTD) for ELC-301. A total of 12 patients are expected to be evaluated at the maximum tolerable dose. In the second step, a total of six patients are treated to frame the treatment dose for continued clinical development.
A new CAR T-cell therapy for the initial treatment of brain tumors with immune enhancement via the iTANK-platform
Glioblastoma (glioblastoma; GBM) is an aggressive form of brain cancer with a very high mortality rate, the expected survival of people diagnosed is about 15 months. In the US alone, approximately 15,000 individuals are affected by GBM and this form of cancer is expected to become more common, mainly due to the lack of effective cures. An aggravating factor in the development of drugs in the central nervous system is to enable the drug to cross the blood-brain barrier. Due to many setbacks in the pharmaceutical industry's attempts to overcome this challenge, GBM is currently treated primarily through surgery and radiation therapy.
ELC-401 targets the tumor antigen IL13Ra2 – a receptor protein that is overrepresented in GBM. In a preclinical study, the company has been able to show that IL13Ra2 is an effective tumor target for iTANK-enhanced CAR T-cells. The study, published in Nature Communications in 2023, evaluated the synthetic receptor underlying ELC-401. The results showed, among other things, that the CAR T-cells had a potent cell-killing effect and prolonged survival in the disease model.
Thanks to iTANK, ELC-401 is also expected to be able to counteract the highly immunosuppressive microenvironment in glioblastoma and mobilize an immune response against other targets in this heterogeneous form of cancer.
ELC-401 is currently in late preclinical evaluation phase and the company is evaluating the optimal route of administration for the CAR T-cell therapy.
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, armed with the company's proprietary iTANK-technology and a trans gene for 4-1BBL. 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.
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.
ELC-100 is currently being tested in a clinical phase I/II-trial, sponsored by Uppsala University, which is planned in two steps (ClinicalTrials.gov Identifier: NCT02749331) where the main goal of step one is to determine safety and the maximum tolerable dose to be tested in step two in an additional 12 patients.
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).