ATC Group: L01XL Antineoplastic cell and gene therapy

Axicabtagene ciloleucel, an engineered autologous T-cell immunotherapy product, binds to CD19 expressing cancer cells and normal B cells. Following anti-CD19 CAR T-cell engagement with CD19 expressing target cells, a sequence of events leads to apoptosis and necrosis of CD19-expressing target cells. Αxicabtagene ciloleucel is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.

Brexucabtagene autoleucel, a CD19-directed genetically modified autologous T-cell immunotherapy, binds to CD19 expressing cancer cells and normal B cells. Following anti-CD19 CAR T-cell engagement with CD19 expressing target cells, the CD28 co-stimulatory domain and CD3-zeta signalling domain activate downstream signalling cascades that lead to T-cell activation, proliferation, acquisition of effector functions and secretion of inflammatory cytokines and chemokines. This sequence of events leads to killing of CD19-expressing cells.

Ciltacabtagene autoleucel is a BCMA-directed, genetically modified autologous T cell immunotherapy, which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells.

Idecabtagene vicleucel is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB costimulatory domain. Antigen-specific activation of idecabtagene vicleucel results in CAR-positive T cell proliferation, cytokine secretion and subsequent cytolytic killing of BCMA-expressing cells.

Lifileucel is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. The specific mechanism of action of lifileucel is unknown.

Lisocabtagene maraleucel is a CD19-directed genetically modified autologous cellular immunotherapy administered as a defined composition to reduce variability in CD8+ and CD4+ T-cell dose. CAR binding to CD19 expressed on the cell surface of tumour and normal B cells induces activation and proliferation of CAR T cells, release of pro-inflammatory cytokines, and cytotoxic killing of target cells.

Nadofaragene firadenovec is a non-replicating adenoviral vector-based gene therapy designed to deliver a copy of a gene encoding a human interferon-alfa 2b (IFNα2b) to the bladder urothelium. Intravesical instillation of nadofaragene firadenovec results in cell transduction and transient local expression of the IFNα2b protein that is anticipated to have anti-tumor effects.

Tabelecleucel is an allogeneic, EBV-specific T-cell immunotherapy which targets and eliminates EBV-infected cells in an HLA-restricted manner. Tabelecleucel has an equivalent mechanism of action to that demonstrated by endogenous circulating T cells in the donors from which the medicinal product is derived. The T-cell receptor of each clonal population within tabelecleucel recognises an EBV peptide in complex with a specific HLA molecule on the surface of target cells (the restricting HLA allele) and allows the medicinal product to exert cytotoxic activity against the EBV-infected cells.

Talimogene laherparepvec is an oncolytic immunotherapy that is derived from HSV-1. Talimogene laherparepvec has been modified to replicate within tumours and to produce the immune stimulatory protein human GM-CSF. Talimogene laherparepvec causes the death of tumour cells and the release of tumour-derived antigens.

Tisagenlecleucel is an autologous, immunocellular cancer therapy which involves reprogramming a patient’s own T cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19 expressing cells.