CAR T-cell therapies have shown transformational potential for the treatment of liquid tumours. The recent approval of Bristol Myers Squibb’ multiple myeloma CAR T drug Abecma brings the number of CAR T therapy approvals up to five, with three coming during the last year alone. However, despite the remarkable innovation and excitement surrounding this technology, major challenges still remain, especially with regard to solid tumour treatments. Swedish gene therapy company Elicera may have what it takes to get past these hurdles.
Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary type of immunotherapy that offers the potential for better and more personalised cancer treatments. The therapy is based on the use of cells from the patient’s immune system to fight certain kinds of cancer. The treatment process involves the removal of some T-cells (a type of white blood cell that attacks foreign molecules in the body) from a patient. These cells are then genetically re-programmed in the lab to identify a patient’s cancer cells and destroy them.
While decades of research have gone into CAR T discovery, it is only recently that the technology has taken off in terms of market approvals.
Five CAR T approvals so far
In 2017, the FDA approved the first two CAR T treatments: Novartis’ Kymriah and Gilead Science’s Yescarta, both for the treatment of B-cell lymphoma. A year later, the American Society of Clinical Oncology (ASCO) announced CAR T cell therapy as 2018’s Advance of the Year. Since then, in the past year alone, the USA has seen three more CAR T therapy approvals: Gilead Science’s Tecartus for the treatment of mantle cell lymphoma, Bristol Myers Squibb (BMS)’s Breyanzi, the third CAR T treatment for B-cell lymphoma, and, most recently (March 26, 2021), BMS’s Abecma, the first CAR T Cell therapy for multiple myeloma.
The solid tumour conundrum
When looking at these approvals, one trend is clear: so far, all CAR T treatments are targeting liquid tumours, i.e., tumours of the blood, not solid tumours like breast, lung or pancreatic cancer. This is no coincidence as all approved CAR T treatments are limited to one specific target – CD19, an antigen typically found on the surface of B-cells, a type of white blood cell, and thus only found in specific blood cancers and not solid tumours.
The challenges in treating solid tumours with CAR T-cells lie mainly in two major factors: solid tumours have several cell surface antigens to target, making it difficult for CAR T-cells to find and attack such tumours since they can only target one antigen, and solid tumours present a hostile microenvironment for CAR T-cells, making them less effective. However, research is ongoing to discover and develop new and better CAR T-cells able to target more than one antigen and resist the hostile microenvironment of solid tumours.
Elicera Therapeutics delivers with iTANK platform
A prime example of such research is found in Sweden, where gene therapy start-up Elicera Therapeutics is developing immunotherapy solutions based on both CAR T-cells and oncolytic viruses. The company is working with versions of the latest (fourth) generation of CAR T-cells, which is designed to improve cell proliferation and survival within the body and give a boosted overall immune response. To put this into context, the currently approved CAR T-cell therapies are all second generation, a major reason why they target only liquid tumours.
However, Elicera’s CAR Ts include the company’s own iTANK (ImmunoTherapies Activated with NAP for efficient Killing) platform, a technology platform that optimises these therapies even further by giving them the ability to bind to more than one antigen. For a more detailed overview of the company, read here. Preclinical data suggests that the iTANK platform helps CAR T-cells inhibit tumour growth and prolong survival compared to conventional CAR Ts and can per se attract co-development and licensing opportunities.
Potential in both liquid and solid tumours
Elicera has two ongoing projects with iTANK-enforced CAR T-cells: ELC-301 and ELC-401. ELC-301 is being developed for the treatment of B-cell lymphoma, and compared to the approved drugs mentioned above, ELC-301 targets CD20 instead of CD19. Unfortunately, currently available data suggests that more than 50 per cent of all patients with B-cell lymphoma treated with conventional CD19 CAR T-cells lack a sustained complete response, thus requiring additional treatments to compensate. By targeting CD20, which is over-expressed in B-cell lymphoma, and with the addition of the iTANK platform, Elicera’s ELC-301 has the potential to be a gamechanger for B-cell lymphoma patients.
Meanwhile, ELC-401 has glioblastoma multiforme (GBM) as its initial indication, so a solid tumour. Thanks to having the protein IL13Ra2 as a target, which is expressed on a number of solid tumors, ELC-401 has the potential to target a wide selection of solid tumours, making it a very versatile candidate.
Strong market potential for Elicera’s candidates
According to Roots Analysis, the global market for CAR Ts is expected to reach 14 BUSD by 2030. There are an estimated 115 companies developing CAR T technology, the majority being in the USA and in China. Very few companies are developing CAR T cells in Europe; in fact, Elicera is the only company developing them in Sweden.
As we see more and more CAR T-based treatments being approved and considering that Elicera’s candidates are highly optimised versions of CAR T treatments currently on the market thanks to the company’s iTANK platform, the market potential for Elicera’s candidates is hard to ignore. BioStock will continue to follow Elicera as it progresses on its CAR T development journey.The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.