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FORNY20-FORNY2020

KVAL: Commercial development of CAR T-cells targeting CD37 or IgKappa/CD19

Alternative title: Commercial development of CAR T-cells targeting CD37 or IgKappa/CD19

Awarded: NOK 0.43 mill.

Project Number:

323740

Project Period:

2021 - 2021

Funding received from:

Organisation:

This project aims at developing two new CAR T cell therapy solutions for patients with Non-Hodgkin Lymphoma (NHL). This is an illness that can affect both young children and adults. The current prognosis has improved with the chemotherapy regimen, R-CHOP and CAR T cell therapy targeting B-cell antigen CD19. Unfortunately not all the patients respond well to these treatments and their illness progresses, sometimes with a deadly outcome. The first problem that this project aims to overcome is to treat patients that have failed to respond to the standing CAR T-cell therapy solution, Kymriah or Yescarta which target CD19. It will do this through the CAR T cell targeting CD37, an alternative cell surface marker to CD19 in NHL cancer. The benefit with CD37 is that it can still be expressed on the cancer cells, after the CD19 cell surface target has disappeared. The second problem this project aims to overcome is to give CAR T-cell therapy to Lymphoma patients that have the sub-group of B-cell receptor type called IgKappa+. These patients will be able to retain a stronger immune system, resisting infections and other cancers. The qualification project has led to successful licensing of the CD37 CAR T-cell technology to an international cell therapy company. We have also successfully achieved granted patents in Europe and US during the project period. The IgKappa/CD19 technology has been further developed and discussed with leading induustry players, who have provided important development feedback while expressing interest. We plan to follow up the interest when we have generated the requested data.

Det ene produktet (CD37 CAR) har blitt utlisensiert og lisenstaker planlegger en multisenter klinisk studie for å teste konseptet i mennesker. OUS forventes å være ett av studiesetene. Basert på industritilbakemelding under prosjektet, planlegges det videre verifisering av det andre produktet/konseptet (IgKappa/CD19 CAR) under prosjektet for å styrke sjansene for fremtidig kommersialisering.

Two CAR-T cell inventions were received at Inven2 in 2015 and 2018, targeting CD37 and IgKappa, respectively. These CAR-T cells developed from OUS-developed antibodies, were the first CAR-T cells to be developed in Norway. Both projects have been patent-filed and are undergoing pre-clinical development at the Unit for Cell Therapy of Oslo University Hospital. The research team has focused the treatment of these two targets on Lymphoma, mainly on Non-Hodgkin lymphoma (NHL), where there is still an unmet need for new and innovative treatment. The disease affects a substantial patient population per year and is an important cause of mortality worldwide. Current treatment approaches involve the administration of R-CHOP which includes the monoclonal antibody Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride (hydroxydaunomycin), Oncovin and Prednisone. There are numerous drawbacks with the drugs and complete responses are frequently not achievable. The most specific and targeted therapy would be Rituximab, an antibody targeting CD20, however, the patient's own B cells will eventually down-regulate the drug target and develop drug resistance. Moreover, the immunosuppressive effect on the patient's weakened immune system will contribute to further worsening of the patient's overall state. More recently, CAR T-cell therapy has been developed for treating NHL. Kymriah (Novartis) and Yescarta (Gilead) were both launched in USA and EU for the treatment of relapsed B cell lymphoma, such as diffuse large B-cell lymphoma, DLBCL and pediatric acute lymphoblastic leukaemia, ALL. The current CAR T-cell treatment aims at another target on B cells, CD19. This therapy also has the disadvantage of target down-regulation and relapse. For this problem, OUS scientists have invented the CD37 CAR-T, which targets CD37, widely expressed on B cells, even after they down-regulated CD20 and/or CD19. The CAR-T targeting IgKappa has the advantage of sparing all IgKappa negative cells.

Funding scheme:

FORNY20-FORNY2020