Magnus Essand's research projects on cancer immunotherapy

CAR-T cell therapy

Chimeric antigen receptor (CAR) T cell therapy is a complex treatment regimen involving reprogramming of patient-derived T cells ex vivo before returning these cells to the patient. Our research group has both preclinical and clinical projects on CAR-T cells.

Hematological malignancies

Microscope image of a CAR-T cell
The image displays a CAR-T cell with the
CAR molecule stained in red.

CD19-directed CAR-T cell therapies are today approved for B-cell acute lymphoblastic leukemia and B-cell lymphomas. Treatment is effective but many patients relapse after treatment and the recurrent tumor is then often negative for CD19 expression. This so-called antigen-loss is probably due to selective pressure induced by the treatment. Our main focus is on developing CAR-T cells targeting CD20, that are armed with the Neutrophil-Activating Protein (NAP), derived from Helicobacter pylori, to counteract antigen-loss. Such CAR20(NAP)-T cells are currently entering clinical evaluation for patients who not eligible to receive approved CD19 CAR-T cell products and patients relapsing from approved CD19 CAR-T cell treatment.

Glioblastoma

Antigen heterogeneity within solid tumours, such as glioblastoma, makes it difficult to develop CAR-T cells that target and kill all tumour cells within a tumour. Furthermore, these tumours exhibit an immunosuppressive microenvironment that dampens the activity of CAR-T cells. We have developed CAR-T cells directed against IL13Ra2, an antigen commonly expressed by glioblastoma. IL13Ra2 expression is however heterogenous. By arming IL13Ra2-directed CAR-T cells with NAP we have shown in animal models that we are able to evoke bystander activation of endogenous tumour antigen-specific T cells that can target also “CAR-target antigen-negative” tumour cells and thereby improve outcome in experimental models.

Oncolytic virus and viral vector for immunotherapy of cancer

Oncolytic viruses can induce immunogenic cancer cell death releasing endogenous alarm signals for the immune system leading to activation of anti-tumour T cell responses. They can therefore pave the way for effective immune checkpoint blockade.

We are developing oncolytic viruses armed with factors for recruitment and activation of dendritic cells that upon activation can take up tumour antigen from killed tumour cells and cross-present antigenic epitopes to prime cytolytic T cells. We are also developing viral vectors encoding factors able to induce tertiary lymphoid structures in tumour vessels and antigen-presenting niches in the tumour microenvironment for local activation of antigen-specific T cells.

Oncolytic viruses and viral vectors are made specific for recruitment to tumours through virus capsid modification and oncolytic viruses are made specific for replication inside tumour cells through insertion of specific gene regulatory elements. We are currently evaluating a neuroendocrine-specific adenovirus for patients with neuroendocrine cancer patients and are planning for clinical trials with armed oncolytic viruses and adeno-associated viral vectors.

Last modified: 2023-01-30