Camidanlumab tesirine

Last updated
Camidanlumab tesirine
Monoclonal antibody
Type ?
Source Human
Target CD25
Clinical data
Other namesADCT-301
ATC code
  • none
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6548H10150N1732O2038S42
Molar mass 147091.83 g·mol−1

Camidanlumab tesirine (Cami-T or ADCT-301) is an antibody-drug conjugate (ADC) composed of a human antibody that binds to the protein CD25, conjugated to a pyrrolobenzodiazepine dimer toxin. The experimental drug, developed by ADC Therapeutics is being tested in clinical trials for the treatment of B-cell Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma (NHL), and for the treatment of B-cell acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Contents

Technology

The human monoclonal antibody is conjugated via a cleavable linker to a cytotoxic (anticancer) pyrrolobenzodiazepine (PBD) dimer. The antibody binds to CD25, which is the alpha chain of the interleukin 2 receptor IL2RA. This molecule is expressed mainly on activated T- and B-cells, both of which are types of white blood cells that play a role in the human immune system. CD25 is over-expressed in a wide range of hematological malignancies, such as leukemias and lymphomas. [1] [2] After binding to a CD25-expressing cell, the antibody is internalized into the cell where enzymes release the cytotoxic drug. PBD dimers work by crosslinking specific sites of the DNA, blocking the cancer cells’ division that cause the cells to die. As a class of DNA-crosslinking agents they are significantly more potent than systemic chemotherapeutic drugs. [3]

Clinical trials

Two phase I trials are evaluating the drug in patients with relapsed or refractory Hodgkin’s and non-Hodgkin’s lymphoma and relapsed or refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia. [4] [5] At the 59th American Society of Hematology (ASH) Annual Meeting, interim results from a Phase I, open-label, single agent dose-escalating study designed to evaluate the treatment of camidanlumab tesirine in relapsed or refractory Hodgkin’s or non-Hodgkin’s lymphoma were presented. Among the patients enrolled at the time of the data cutoff the overall response rate was 78% (including a 44% complete response rate) in patients with relapsing or refractory Hodgkin’s lymphoma. [6]

Related Research Articles

<span class="mw-page-title-main">Gemtuzumab ozogamicin</span>

Gemtuzumab ozogamicin, sold under the brand name Mylotarg, is an antibody-drug conjugate that is used to treat acute myeloid leukemia.

The interleukin-3 receptor (CD123) is a molecule found on cells which helps transmit the signal of interleukin-3, a soluble cytokine important in the immune system.

<span class="mw-page-title-main">Inotuzumab ozogamicin</span>

Inotuzumab ozogamicin, sold under the brand name Besponsa, is an antibody-drug conjugate medication used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Lintuzumab (SGN-33) is a humanized monoclonal antibody used in the treatment of cancer. The drug had been developed by Seattle Genetics as a treatment for acute myeloid leukemia (AML), a condition which results in the deaths of 9,000 people a year in the United States. Lintuzumab targets the CD33 protein, which is expressed in AML and other myeloproliferative diseases, but does not appear in abundance on normal cells.

<span class="mw-page-title-main">CD135</span> Protein-coding gene in the species Homo sapiens

Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).

<span class="mw-page-title-main">Lestaurtinib</span> Chemical compound

Lestaurtinib is a tyrosine kinase inhibitor structurally related to staurosporine. This semisynthetic derivative of the indolocarbazole K252a was investigated by Cephalon as a treatment for various types of cancer. It is an inhibitor of the kinases fms-like tyrosine kinase 3 (FLT3), Janus kinase 2 (JAK2), tropomyosin receptor kinase (trk) A (TrkA), TrkB and TrkC.

Blinatumomab, sold under the brand name Blincyto, is a biopharmaceutical medication used as a second-line treatment for Philadelphia chromosome-negative relapsed or refractory acute lymphoblastic leukemia. It belongs to a class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets the CD19 antigen present on B cells. In December 2014, it was approved by the US Food and Drug Administration under the accelerated approval program; marketing authorization depended on the outcome of clinical trials that were ongoing at the time of approval.

Milatuzumab is an anti-CD74 humanized monoclonal antibody for the treatment of multiple myeloma non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

<span class="mw-page-title-main">Blastic plasmacytoid dendritic cell neoplasm</span> Medical condition

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy. It was initially regarded as a form of lymphocyte-derived cutaneous lymphoma and alternatively named CD4+CD56+ hematodermic tumor, blastic NK cell lymphoma, and agranular CD4+ NK cell leukemia. Later, however, the disease was determined to be a malignancy of plasmacytoid dendritic cells rather than lymphocytes and therefore termed blastic plasmacytoid dendritic cell neoplasm. In 2016, the World Health Organization designated BPDCN to be in its own separate category within the myeloid class of neoplasms. It is estimated that BPDCN constitutes 0.44% of all hematological malignancies.

Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seattle Genetics in the US.

<span class="mw-page-title-main">Midostaurin</span> Chemical compound

Midostaurin, sold under the brand name Rydapt & Tauritmo both by Novartis, is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus.

Lirilumab (INN) is a human monoclonal antibody designed for the treatment of cancer. It binds to KIR2DL1/2L3.

<span class="mw-page-title-main">Vadastuximab talirine</span>

Vadastuximab talirine is an antibody-drug conjugate (ADC) directed to CD33 (siglec-3) which is a transmembrane receptor expressed on cells of myeloid lineage. The experimental drug, being developed by Seattle Genetics, was in clinical trials for the treatment of acute myeloid leukemia (AML).

Seagen Inc. is an American biotechnology company focused on developing and commercializing innovative, empowered monoclonal antibody-based therapies for the treatment of cancer. The company, headquartered in Bothell, Washington, is the industry leader in antibody-drug conjugates or ADCs, a technology designed to harness the targeting ability of monoclonal antibodies to deliver cell-killing agents directly to cancer cells. Antibody-drug conjugates are intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy, while potentially enhancing antitumor activity.

ImmunoGen, Inc. is a biotechnology company focused on the development of antibody-drug conjugate (ADC) therapeutics for the treatment of cancer. ImmunoGen was founded in 1981 and is headquartered in Waltham, Massachusetts.

FLAG is a chemotherapy regimen used for relapsed and refractory acute myeloid leukemia (AML). The acronym incorporates the three primary ingredients of the regimen:

  1. Fludarabine: an antimetabolite that, while not active toward AML, increases formation of an active cytarabine metabolite, ara-CTP, in AML cells;
  2. Arabinofuranosyl cytidine : an antimetabolite that has been proven to be the most active toward AML among various cytotoxic drugs in single-drug trials; and
  3. Granulocyte colony-stimulating factor (G-CSF): a glycoprotein that shortens the duration and severity of neutropenia.

Denintuzumab mafodotin is a humanized monoclonal antibody-drug conjugate designed for the treatment of CD19-positive acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma. It consists of an anti-CD19 mAb linked to monomethyl auristatin F (MMAF), a cytotoxic agent. This drug was developed by Seattle Genetics.

<span class="mw-page-title-main">Loncastuximab tesirine</span>

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

Brexucabtagene autoleucel, sold under the brand name Tecartus, is a cell-based gene therapy medication for the treatment of mantle cell lymphoma (MCL) and acute lymphoblastic leukemia (ALL).

<span class="mw-page-title-main">Thomas A. Waldmann</span> American immunologist (1930–2021)

Thomas A. Waldmann was an American immunologist who has worked on therapeutic monoclonal antibodies to the IL-2 receptor, Interleukin 15 (IL-15), and Adult T-cell Leukemia (ATL). Until the week he died, he was an active distinguished investigator at the Lymphoid Malignancies Branch of the National Cancer Institute.

References

  1. Schnell R, Vitetta E, Schindler J, Barth S, Winkler U, Borchmann P, et al. (August 1998). "Clinical trials with an anti-CD25 ricin A-chain experimental and immunotoxin (RFT5-SMPT-dgA) in Hodgkin's lymphoma". Leukemia & Lymphoma. 30 (5–6): 525–37. doi:10.3109/10428199809057565. PMID   9711915.
  2. Nakase K, Kita K, Miwa H, Nishii K, Shikami M, Tanaka I, et al. (February 2007). "Clinical and prognostic significance of cytokine receptor expression in adult acute lymphoblastic leukemia: interleukin-2 receptor alpha-chain predicts a poor prognosis". Leukemia. 21 (2): 326–32. doi: 10.1038/sj.leu.2404497 . PMID   17205058.
  3. "Pyrrolobenzodiazepine". adcreview.com.
  4. Clinical trial number NCT02432235 for "Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma" at ClinicalTrials.gov
  5. Clinical trial number NCT02588092 for "Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)" at ClinicalTrials.gov
  6. "Interim Results from a Phase 1 Study of ADCT-301 (Camidanlumab Tesirine) Show Promising Activity of a Novel Pyrrolobenzodiazepine-Based Antibody Drug Conjugate in Relapsed/Refractory Hodgkin/Non-Hodgkin Lymphoma" (PDF). adctherapeutics.com. Archived from the original (PDF) on 2018-03-08. Retrieved 2018-01-23.