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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
177Lu-Tetraxetan-Tetulomab (BetalutinTM) is based on a murine monoclonal antibody discovered at the Norwegian Radium Hospital and is now being developed by Nordic Nanovector. It is targeted to the CD37 glycoprotein found on the surface of mature malignant and nonmalignant human B cells, and is being used as a tumor-targeting carrier for both radioactive and cytotoxic payloads for the treatment of hematological cancers. BetalutinTM itself consists of the CD37-targeting monoclonal antibody tetulomab conjugated to the short-lived beta-emitting Lutetium radionuclide 177Lu (Figure 7.41). Structure of the Antibody-Radionuclide Conjugate 177Lu-Tetraxetan-Tetulomab (Betalutin™) (Figure reprinted with permission from Nordic Nanovector ©).
Treatment of Relapsed B Cell Lymphomas with High Dose Radioimmunotherapy and Bone Marrow Transplantation
Published in David M. Goldenberg, Cancer Therapy with Radiolabeled Antibodies, 1995
Oliver W. Press, Janet F. Eary, Frederick R. Appelbaum, Irwin D. Bernstein
The utility of high-dose RAIT for the treatment of recurrent B-cell lymphomas has been investigated in Seattle using 131I-labeled anti-B-cell antibodies targeting the CD20 (1F5, B1) and CD37 (MB1) antigens.10,15
Cardiovascular Complications of Immune Checkpoint Inhibitors
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Sultan Tousif, Anand Prakash Singh, Prachi Umbarkar, Hind Lal
The co-stimulatory signal, which regulates the recognition of antigens by the TCR, can also be termed as an immune checkpoint. Immune checkpoints can be either costimulatory or co-inhibitory. CD27, CD37, CD40, GITR (CD278), and OX40 (CD134) are co-stimulatory immune checkpoints that fall under the tumor necrosis factor (TNF) superfamily, whereas CD28 and ICOS stimulatory signals belong to the B7-CD28 superfamily. Programmed death-1 (PD-1), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), adenosine A2A receptor (A2AR), indoleamine 2,3-dioxygenase (IDO), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase isoform 2 (NOX-2), and V-domain Ig suppressor of T cell activation (VISTA) are considered as co-inhibitory immune checkpoints. On exposure to pathogens, adaptive immune cells are activated by antigen presentation and the signals induced by co-stimulatory immune checkpoints to protect the healthy tissues from damage [1]. The inhibitory immune checkpoint competes with the co-stimulatory molecule to diminish host immunity during pathogenic attacks, cancer, or other deadly diseases that hijack the host immune system [2]. This concerted action of co-stimula-tory and inhibitory signals ensures that the immune system does not keep firing once the offending pathogen or disease stimulus has been neutralized. Pathogens and cancer cells have devised smart ways to exploit such inhibitory immune checkpoints to evade host immune response [3, 4]. Therefore, immune checkpoint therapy relies on reactivation of immune function by using either an agonist of the co-stimulatory signal or an antagonist of inhibitory immune checkpoint molecules [5].
Myelosuppression in patients treated with 177Lutetium-lilotomab satetraxetan can be predicted with absorbed dose to the red marrow as the only variable
Published in Acta Oncologica, 2021
Johan Blakkisrud, Ayca Løndalen, Jostein Dahle, Anne Catrine Martinsen, Arne Kolstad, Caroline Stokke
[177Lutetium]Lu-lilotomab satetraxetan (Betalutin®) is a RIT targeting the CD37-antigen [7]. CD37 is expressed on mature B-cells and the majority of B-cell NHL, and previous studies of CD37-targeting treatments have shown promising results in both clinical and preclinical studies [8–13]. Targeting CD37 may be an especially promising alternative for relapsed indolent NHL patients, as previous treatment with anti-CD20 drugs can lead to resistance against further anti-CD20 treatment [14]. This RIT is currently being investigated in three trials, including the multi-center, non-randomized, open-label, first in human phase 1/2a-study LYMRIT-37-01 (NCT01796171). The radionuclide carried by [177Lu]Lu-lilotomab satetraxetan is 177Lu. This radionuclide is, similarly to 131I and 90Y, also a 177Lu allow in-depth studies of biodistribution and consequently the absorbed dose to different tissues in each patient post-treatment.
Investigational therapies targeting CD37 for the treatment of B-cell lymphoid malignancies
Published in Expert Opinion on Investigational Drugs, 2018
Magdalena Witkowska, Piotr Smolewski, Tadeusz Robak
CD37 is a member of the transmembrane 4 superfamily of tetraspanin proteins. It consists of four potential membrane-spanning regions, two extracellular loops, and short intracytoplasmatic tails [4]. CD37 forms complexes with other tetraspanins, such as CD53, CD81, CD82, and class II glycoprotein, on the surface of B cells, which might represent an ion channel or transporter [5]; this results in the formation of multiprotein complexes called tetraspanin microdomains, also known as tetraspanin webs, on the cell surface.
Harnessing immunotherapy for pediatric T-cell malignancies
Published in Expert Review of Clinical Immunology, 2020
Caroline Diorio, David T. Teachey
Finally, an anti-CD37 CAR-T has recently been developed, and shown to be active in both B- and T- cell lymphomas[125]. This CAR-T did not appear to be vulnerable to fratricide. Intriguingly, the authors also utilized a bispecific CAR-T that targeted both CD37 and CD19[125]. Bispecific CAR-T targeting dual T-cell specific markers have not yet been developed, to our knowledge.