scholarly journals Towards Possible Cure of Cancer by Immunotherapy of Minimal Residual Disease Using Intentionally Mismatched Donor Lymphocytes

2020 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Mismatched Donor ◽  
Minimal Residual ◽  
Donor Lymphocytes

Targeted immunotherapy with intentionally mismatched rIL-2 activated donor lymphocytes in an attempt to eliminate minimal residual disease in patients with high-risk metastatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21175-21175
Author(s):  
S. Slavin ◽  
R. Or ◽  
L. Dray ◽  
S. Samuel ◽  
A. Ackerstein ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Solid Tumors ◽  
Minimal Residual Disease ◽  
Hematological Malignancies ◽  
Residual Disease ◽  
Bispecific Antibodies ◽  
Minimal Residual ◽  
Donor Lymphocytes

21175 Background: Graft-versus-leukemia and graft-versus-tumor (GVT) effects following stem cell transplantation are well established, however, procedure related toxicity and mortality are unavoidable. In addition to limited efficacy following stem cell transplantation (SCT), graft-versus-host disease (GVHD) is unavoidable. Our protocol was designed to induce more potent anti-cancer immunotherapy by rIL-2 activated intentionally mismatched donor lymphocytes (MDL) at the stage of minimal residual disease (MRD) outpatient procedure with no SCT avoiding GVHD. Methods: Optimizing MDL was accomplished by cyclophosphamide 1,500 mg/m2 and 2 injections of alpha interferon (3x106IU) for more effective immunotherapy, aiming for depletion of regulatory T cells, followed by infusion of haploidentically mismatched lymphocytes activated with rIL-2 (6,000 IU/ml) for 4 days. On the day of cell infusion, patients received rIL-2 6x106 IU subcutaneously outpatient for 5 days. Results: A total of 41 (age 5–73, median 52) high risk patients were included: metastatic breast 13; colorectal 3; gastric 3; pancreatic 3; melanoma 3; head & neck 3; glioblastoma 2; and 6 with other solid tumors. Five patients had resistant hematological malignancies: multiple myeloma 2; non-Hodgkin's lymphoma 2 and Hodgkin's disease 1. 6 patients received lymphocytes with bispecific antibodies for targeted cell-therapy (3 with catumaxomab against CD3 & epithelial cell adhesion molecule (EpCAM); 3 with ertumaxomab directed against CD3 & Her-2/neu WHO toxicity >grade 2 was noted. 14 of evaluable patients are alive. 10/32 with solid tumors are alive, 7 with no evidence of disease > 9–91 (median 17) months (4 breast; 1 squamous cell; 1 head & neck; 1 prostate). Of 5 patients with hematological malignancies 4 are alive and disease free >18–96 (median 46) months. Conclusions: Safe induction of GVT effects may be accomplished by MDL, preferably targeted with bispecific antibodies after cyclophosphamide conditioning lymphocytes are more potent and act faster than matched lymphocytes and GVHD is avoided by rejection of donor lymphocytes. When applied at a stage of MRD, such treatment may result in operational cure. No significant financial relationships to disclose.

ACUTE LEUKEMIAS 2019: Risikofaktor MRD eröffnet neue Perspektiven

2019 ◽  
Vol 10 (04) ◽  
pp. 158-160
Author(s):  
Ulrike Röper
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Individualisierte Therapie ◽  
Acute Leukemias ◽  
Minimal Residual

Weiterentwicklungen in der Molekulardiagnostik ermöglichen zuverlässigere Aussagen zur Differenzialdiagnostik maligner Erkrankungen. Sie sind Meilensteine für eine individualisierte Therapie. Darüber hinaus zeigt sich ihre zunehmende Bedeutung für prognostische Einschätzungen. Die Kontrolle der minimalen Resterkrankung (Minimal Residual Disease; MRD) rückt zunehmend in den Fokus, auch wenn noch viele Fragen zu klären sind.

A mathematical approach to data evaluation with focus on prediction of minimal residual disease in pediatric ALL

2012 ◽  
Vol 224 (03) ◽  
Author(s):  
A Torge ◽  
M Zimmermann ◽  
A Möricke ◽  
R Köhler ◽  
A Schrauder ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Data Evaluation ◽  
Mathematical Approach ◽  
Pediatric All ◽  
Minimal Residual
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