scholarly journals Monoclonal antibodies in acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (26) ◽  
pp. 4010-4016 ◽  
Author(s):  
Elias Jabbour ◽  
Susan O’Brien ◽  
Farhad Ravandi ◽  
Hagop Kantarjian
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Median Survival ◽  
Lymphoblastic Leukemia ◽  
Complete Response ◽  
Surface Antigens ◽  
Leukemic Cells ◽  
The Novel ◽  
Cure Rates

Abstract With modern intensive combination polychemotherapy, the complete response (CR) rate in adults with acute lymphoblastic leukemia (ALL) is 80% to 90%, and the cure rate is 40% to 50%. Hence, there is a need to develop effective salvage therapies and combine novel agents with standard effective chemotherapy. ALL leukemic cells express several surface antigens amenable to target therapies, including CD20, CD22, and CD19. Monoclonal antibodies target these leukemic surface antigens selectively and minimize off-target toxicity. When added to frontline chemotherapy, rituximab, an antibody directed against CD20, increases cure rates of adults with Burkitt leukemia from 40% to 80% and those with pre-B ALL from 35% to 50%. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has resulted in marrow CR rates of 55% and a median survival of 6 to 7 months when given to patients with refractory-relapsed ALL. Blinatumomab, a biallelic T cell engaging the CD3-CD19 monoclonal antibody, also resulted in overall response rates of 40% to 50% and a median survival of 6.5 months in a similar refractory-relapsed population. Other promising monoclonal antibodies targeting CD20 (ofatumumab and obinutuzumab) or CD19 or CD20 and bound to different cytotoxins or immunotoxins are under development. Combined modalities of chemotherapy and the novel monoclonal antibodies are under investigation.

scholarly journals Serotherapy of acute lymphoblastic leukemia with monoclonal antibody

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 141-152 ◽  
Author(s):  
J Ritz ◽  
JM Pesando ◽  
SE Sallan ◽  
LA Clavell ◽  
J Notis-McConarty ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chemotherapeutic Agents ◽  
Leukemic Cells ◽  
Antigenic Modulation ◽  
Multiple Intravenous Infusions ◽  
Marrow Cellularity

Abstract We tested the efficacy of passive serotherapy in the treatment of acute lymphoblastic leukemia in four patients who had relapsed while receiving standard chemotherapeutic agents. Each patient received multiple intravenous infusions of J-5 monoclonal antibody specific for common acute lymphoblastic leukemia antigen (CALLA). In the three patients with circulating leukemic cells, there was a rapid decrease in circulating blasts that began immediately after antibody infusion, but not all leukemic cells were cleared, and remaining cells appeared to be resistant to further serotherapy. Although J-5 antibody was also demonstrable on bone marrow lymphoblasts immediately after antibody infusion in one patient, there was no change in bone marrow cellularity or differential during serotherapy. Analysis of the cell surface phenotype of leukemic cells during serotherapy and in vitro studies with patient cells suggests that resistance to serotherapy was mediated in part by antigenic modulation of CALLA in response to J-5 antibody.

scholarly journals Acute lymphoblastic leukemia in infants: evidence for B cell origin of disease by use of monoclonal antibody phenotyping

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 975-978 ◽  
Author(s):  
PA Dinndorf ◽  
GH Reaman
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
B Cell Development ◽  
Lymphoid Cells ◽  
Hla Dr ◽  
Cell Commitment

Abstract Since the prognosis of infants with acute lymphoblastic leukemia (ALL) is so poor, it has been suggested that these leukemias may not be lymphoid in origin, but may originate from stem cell, myeloid, or megakaryocytic progenitors. Alternately it has been hypothesized that these leukemias originate in lymphoid cells at the earliest stages of B cell development. Another possibility is that these leukemias may be of more than one lineage. Therefore we examined leukemic blasts from 12 infants with ALL using monoclonal antibodies to myeloid and lymphoid differentiation antigens. The majority of specimens expressed HLA/DR and reacted with B4 (CD19) but failed to react with stem cell, myeloid, megakaryocytic, or T cell associated antibodies. These results support the speculation that the majority of these leukemias arise in cells at the earliest stages of B cell commitment, and are not of a myeloid or biphenotypic nature.

scholarly journals Serotherapy of acute lymphoblastic leukemia with monoclonal antibody

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 141-152
Author(s):  
J Ritz ◽  
JM Pesando ◽  
SE Sallan ◽  
LA Clavell ◽  
J Notis-McConarty ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chemotherapeutic Agents ◽  
Leukemic Cells ◽  
Antigenic Modulation ◽  
Multiple Intravenous Infusions ◽  
Marrow Cellularity

We tested the efficacy of passive serotherapy in the treatment of acute lymphoblastic leukemia in four patients who had relapsed while receiving standard chemotherapeutic agents. Each patient received multiple intravenous infusions of J-5 monoclonal antibody specific for common acute lymphoblastic leukemia antigen (CALLA). In the three patients with circulating leukemic cells, there was a rapid decrease in circulating blasts that began immediately after antibody infusion, but not all leukemic cells were cleared, and remaining cells appeared to be resistant to further serotherapy. Although J-5 antibody was also demonstrable on bone marrow lymphoblasts immediately after antibody infusion in one patient, there was no change in bone marrow cellularity or differential during serotherapy. Analysis of the cell surface phenotype of leukemic cells during serotherapy and in vitro studies with patient cells suggests that resistance to serotherapy was mediated in part by antigenic modulation of CALLA in response to J-5 antibody.

scholarly journals Recategorizing childhood acute lymphoblastic leukemia with monoclonal antibodies to human T cells

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1135-1137
Author(s):  
PM Sondel ◽  
W Borcherding ◽  
NT Shahidi ◽  
DJ Ganick ◽  
JC Schultz ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Cell Leukemia ◽  
Differentiation Markers ◽  
Human T Cells ◽  
Thymocyte Differentiation ◽  
Normal Differentiation

The lymphoblasts of three patients with childhood acute lymphoblastic leukemia (ALL) were analyzed for their immunologic surface markers. Blasts from two of these patients did not form rosettes with sheep erythrocytes and the third did so marginally, suggesting these patients had non-T-cell leukemia. These blasts were also tested with monoclonal antibodies that detect thymocyte differentiation markers, and all three patients were highly reactive with at least two of these reagents. We anticipate the availability of multiple standardized monoclonal reagents will necessitate a recategorization of ALL phenotypes. Some of these leukemic phenotypes may not correspond to normal stages of lymphoid differentiation. Therefore, we suggest that it may be inappropriate to attempt to identify and categorize leukemic cells by the pathways of normal differentiation.

scholarly journals Recategorizing childhood acute lymphoblastic leukemia with monoclonal antibodies to human T cells

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1135-1137 ◽  
Author(s):  
PM Sondel ◽  
W Borcherding ◽  
NT Shahidi ◽  
DJ Ganick ◽  
JC Schultz ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Cell Leukemia ◽  
Differentiation Markers ◽  
Human T Cells ◽  
Thymocyte Differentiation ◽  
Normal Differentiation

Abstract The lymphoblasts of three patients with childhood acute lymphoblastic leukemia (ALL) were analyzed for their immunologic surface markers. Blasts from two of these patients did not form rosettes with sheep erythrocytes and the third did so marginally, suggesting these patients had non-T-cell leukemia. These blasts were also tested with monoclonal antibodies that detect thymocyte differentiation markers, and all three patients were highly reactive with at least two of these reagents. We anticipate the availability of multiple standardized monoclonal reagents will necessitate a recategorization of ALL phenotypes. Some of these leukemic phenotypes may not correspond to normal stages of lymphoid differentiation. Therefore, we suggest that it may be inappropriate to attempt to identify and categorize leukemic cells by the pathways of normal differentiation.

scholarly journals Monoclonal Antibodies Specific to the Acute Lymphoblastic Leukemia t(1; 19)-Associated E2A/pbx1 Chimeric Protein: Characterization and Diagnostic Utility

Blood ◽  
1997 ◽  
Vol 89 (8) ◽  
pp. 2909-2914 ◽  
Author(s):  
Bi-Ching Sang ◽  
Liangru Shi ◽  
Peter Dias ◽  
Li Liu ◽  
Jia Wei ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Lymphoblastic Leukemia ◽  
Fusion Protein ◽  
Chromosomal Abnormalities ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Chimeric Protein ◽  
Protein Characterization ◽  
Leukemic Cells ◽  
Childhood All

Abstract Nonrandom chromosomal abnormalities are found in most human malignancies, particularly leukemias and lymphomas. A characteristic t(1; 19) (q23; p13.3) chromosomal translocation is detected in 5% of childhood acute lymphoblastic leukemia (ALL) cases. This translocation results in the formation of a fusion gene, which leads to the expression of an oncogenic E2A/pbx1 protein. Breakpoints in the E2A gene almost invariably occur within a single intron, and the identical portion of PBX1 is joined consistently to exon 13 of E2A in fusion mRNA. In this article, we report the development of monoclonal antibodies against E2A/pbx1 fusion protein using a specific peptide that corresponds to the junction region of the protein. The obtained antibodies recognize specifically the chimeric E2A/pbx1 fusion protein and lack cross-reactivities with E2A and pbx1. Immunohistochemical staining and flow cytometric studies show that these antibodies can distinguish t(1; 19)-positive from t(1; 19)-negative leukemic cells. These results indicate that the obtained E2A/pbx1-specific monoclonal antibodies might prove to be valuable diagnostic reagents and important tools for elucidating the mechanisms involved in oncogenesis and progression of t(1; 19)-positive childhood ALL.

scholarly journals Acute lymphoblastic leukemia in infants: evidence for B cell origin of disease by use of monoclonal antibody phenotyping

Blood ◽  
1986 ◽  
Vol 68 (4) ◽  
pp. 975-978
Author(s):  
PA Dinndorf ◽  
GH Reaman
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
B Cell Development ◽  
Lymphoid Cells ◽  
Hla Dr ◽  
Cell Commitment

Since the prognosis of infants with acute lymphoblastic leukemia (ALL) is so poor, it has been suggested that these leukemias may not be lymphoid in origin, but may originate from stem cell, myeloid, or megakaryocytic progenitors. Alternately it has been hypothesized that these leukemias originate in lymphoid cells at the earliest stages of B cell development. Another possibility is that these leukemias may be of more than one lineage. Therefore we examined leukemic blasts from 12 infants with ALL using monoclonal antibodies to myeloid and lymphoid differentiation antigens. The majority of specimens expressed HLA/DR and reacted with B4 (CD19) but failed to react with stem cell, myeloid, megakaryocytic, or T cell associated antibodies. These results support the speculation that the majority of these leukemias arise in cells at the earliest stages of B cell commitment, and are not of a myeloid or biphenotypic nature.

scholarly journals Colony formation in vitro by leukemic cells in acute lymphoblastic leukemia (ALL)

Blood ◽  
1978 ◽  
Vol 52 (4) ◽  
pp. 712-718 ◽  
Author(s):  
SD Smith ◽  
EM Uyeki ◽  
JT Lowman
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Cells ◽  
Lymphoblastic Leukemia ◽  
Lymphoid Cells ◽  
Assay System ◽  
Leukemic Cells ◽  
Specific Cell ◽  
Specific Cell Surface

Abstract An assay system in vitro for the growth of malignant lymphoblastic colony-forming cells (CFC) was established. Growth of malignant myeloblastic CFC has been previously reported, but this is the first report of growth of malignant lymphoblastic CFC. Established assay systems in vitro have been very helpful in elucidating the control of growth and differentiation of both normal and malignant bone marrow cells. Lymphoblastic CFC were grown from the bone marrow aspirates of 20 children with acute lymphoblastic leukemia. Growth of these colonies was established on an agar assay system and maintained in the relative hypoxia (7% oxygen) of a Stulberg chamber. The criteria for malignancy of these colonies was based upon cellular cytochemical staining characteristics, the presence of specific cell surface markers, and the ability of these lymphoid cells to grow without the addition of a lymphoid mitogen. With this technique, specific nutritional requirements and drug sensitivities can be established in vitro, and these data may permit tailoring of individual antileukemic therapy.

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