Research Articles An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma

Enthusiasm for the use of antibody-drug conjugates (ADCs) in cancer therapy has risen over the past few years. The success of this therapeutic approach relies on the identification of cell surface antigens that are widely and selectively expressed on tumor cells. Studies have shown that native ALK protein is expressed on the surface of most neuroblastoma cells, providing an opportunity for development of immune-targeting strategies. Clinically relevant antibodies for this target have not yet been developed. Here, we describe the development of an ALK-ADC, CDX-0125-TEI, which selectively targets both wild-type and mutated ALK-expressing neuroblastomas. CDX-0125-TEI exhibited efficient antigen binding and internalization, and cytotoxicity at picomolar concentrations in cells with different expression of ALK on the cell surface. In vivo studies showed that CDX-0125-TEI is effective against ALK wild-type and mutant patient-derived xenograft models. These data demonstrate that ALK is a bona fide immunotherapeutic target and provide a rationale for clinical development of an ALK-ADC approach for neuroblastomas and other ALK-expressing childhood cancers such as rhabdomyosarcomas.
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research

Related Links:

Publication date: Available online 8 March 2019Source: Surgery (Oxford)Author(s): Emma SidebothamAbstractWhile all childhood cancers are rare, the abdomen and pelvis are common sites of origin. After haematological malignancies and intracranial tumours, neuroblastoma is the most common childhood cancer, most often arising in the adrenal gland. The next most common extracranial tumours are Wilms tumour, arising in the kidney (nephroblastoma) and rhabdomyosarcoma that may arise in a variety of sites, typically in the pelvis. Hepatoblastoma, non-Hodgkin lymphoma and germ cell tumours are other abdominal and pelvic tumours see...
Source: Surgery (Oxford) - Category: Surgery Source Type: research
Publication date: April 2019Source: Cancer Epidemiology, Volume 59Author(s): Danny R. Youlden, A. Lindsay Frazier, Sumit Gupta, Kathy Pritchard-Jones, Maria L. Kirby, Peter D. Baade, Adèle C. Green, Patricia C. Valery, Joanne F. AitkenAbstractBackgroundStage of cancer at diagnosis is one of the strongest predictors of survival and is essential for population cancer surveillance, comparison of cancer outcomes and to guide national cancer control strategies. Our aim was to describe, for the first time, the distribution of cases by stage at diagnosis and differences in stage-specific survival on a population basis for ...
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
Conditions:   Neuroblastoma;   Rhabdomyosarcoma;   Ewing Sarcoma Family of Tumors;   Osteosarcoma;   Leukemia;   Central Nervous System Tumor Intervention:   Other: Sampling on blood, bone marrow and cerebrospinal fluid Sponsor:   Institut Curie Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
MYCN is a member of the MYC family of proto-oncogenes. It encodes a transcription factor, MYCN, involved in the control of fundamental processes during embryonal development. The MYCN protein is situated downstream of several signaling pathways promoting cell growth, proliferation and metabolism of progenitor cells in different developing organs and tissues. Conversely, deregulated MYCN signaling supports the development of several different tumors, mainly with a childhood onset, including neuroblastoma, medulloblastoma, rhabdomyosarcoma and Wilms ’ tumor, but it is also associated with some cancers occurring during ...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Review Source Type: research
Conclusion: The study shows increasing childhood cancer cases over the years. Hematological malignancy takes the leading prevalence followed by Wilms tumor and Neuroblastoma. The majority of cases were also discharged without any clinical change that had the only death option. Therefore, the government and the hospital should give emphasis to establish cancer therapy centers and insure accessibility and affordability of chemotherapy drugs.
Source: BMC Research Notes - Category: Research Authors: Source Type: research
More News: Biomedical Science | Brain | Cancer | Cancer & Oncology | Cancer Therapy | Child Development | Childhood Cancer | Neuroblastoma | Neurology | Neuroscience | Rhabdomyosarcoma | Science | Study