Loncastuximab tesirine

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Loncastuximab tesirine
Loncastuximab tesirine.svg
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetCD19
Clinical data
PronunciationLON-kas-TUK-sih-mab TEH-sih-reen
Trade namesZynlonta
Other namesADCT-402, loncastuximab tesirine-lpyl
License data
Routes of
administration
Intravenous
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6544H10048N1718O2064S52
Molar mass147481.45 g·mol−1

Loncastuximab tesirine , sold under the brand name Zynlonta, is a monoclonal antibody conjugate medication used to treat large B-cell lymphoma.[1] It is an antibody-drug conjugate (ADC) composed of a humanized antibody targeting the protein CD19.[1]

Loncastuximab tesirine was approved for medical use in the United States in April 2021.[1][2]

Medical uses

Loncastuximab tesirine is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma.[1]

Technology

The humanized monoclonal antibody is stochastically conjugated via a valine-alanine cleavable, maleimide linker to a cytotoxic (anticancer) pyrrolobenzodiazepine (PBD) dimer.[medical citation needed] The antibody binds to CD19, a protein which is highly expressed on the surface of B-cell hematological tumors[3] including certain forms of lymphomas and leukemias.[medical citation needed] After binding to the tumor cells the antibody is internalized, the cytotoxic drug PBD is released and the cancer cells are killed.[medical citation needed] PBD dimers are generated out of PBD monomers, a class of natural products produced by various actinomycetes. PBD dimers work by crosslinking specific sites of the DNA, blocking the cancer cells’ division that cause the cells to die.[medical citation needed] As a class of DNA-crosslinking agents they are significantly more potent than systemic chemotherapeutic drugs.[4]

Clinical trials

Two phase I trials are evaluating the medication in people with relapsed or refractory B-cell non-Hodgkin’s lymphoma and relapsed or refractory B-cell acute lymphoblastic leukemia.[5] At the 14th International Conference on Malignant Lymphoma interim results from a Phase I, open-label, dose-escalating study designed to evaluate the treatment of loncastuximab tesirine in relapsed or refractory non-Hodgkin’s lymphoma were presented.[6] Among the patients enrolled at the time of the data cutoff the overall response rate was 61% in the total patient population (42% complete response and 19% partial response) and in patients with relapsing or refractory diffuse large B-cell lymphoma (DLBCL) the overall response rate was 57% (43% complete response and 14% partial response).[7][8]

Orphan drug designation

Loncastuximab tesirine was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of diffuse large B-cell lymphoma.[9]

Research

Given its mechanism of action, loncastiximab tesirinine may be appealing in patients ineligible for CAR-T cell therapy.[10]

References

  1. ^ a b c d e "Zynlonta- loncastuximab tesirine injection, powder, lyophilized, for solution". DailyMed. Retrieved 1 June 2021.
  2. ^ "Drug Approval Package: Zynlonta". U.S. Food and Drug Administration (FDA). 24 May 2021. Retrieved 1 June 2021.
  3. ^ Wang K, Wei G, Liu D (November 2012). "CD19: a biomarker for B cell development, lymphoma diagnosis and therapy". Experimental Hematology & Oncology. 1 (1): 36. doi:10.1186/2162-3619-1-36. PMC 3520838. PMID 23210908.
  4. ^ "Pyrrolobenzodiazepine". ADC Review.
  5. ^ Clinical trial number NCT02669017 for "ADCT-402 in B-NHL" at ClinicalTrials.gov
  6. ^ Kahl B, Hamadani M, Caimi PF, Reid EG, Havenith K, He S, Feingold JM, O'Connor O (June 2017). "First clinical results of ADCT‐402, a novel pyrrolobenzodiazepine-based antibody drug conjugate (ADC), in relapsed/refractory B‐cell linage NHL" (PDF). Hematol Oncol. 35 (S2): 49–51. doi:10.1002/hon.2437_33.
  7. ^ "First clinical results of ADCT-402". ADC Review. 16 June 2017.
  8. ^ Bainbridge K (3 July 2017). "Grandfather fighting deadly cancer reveals scans of tumors after testing new drug". Mirror.
  9. ^ "Loncastuximab tesirine Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 8 June 2017. Retrieved 1 June 2021.
  10. ^ Perrone, Salvatore; Lopedote, Paolo; Levis, Mario; Di Rocco, Alice; Smith, Stephen Douglas (2022-02-21). "Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy". Expert Review of Hematology: 1–18. doi:10.1080/17474086.2022.2044778. ISSN 1747-4086. PMID 35184664. S2CID 247010986.

External links