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Antibodies for NHL

  

Treatments > Antibodies (monoclonal) for Lymphomas

Last update: 05/25/2008

TOPIC SEARCH: PubMed: Monoclonal Antibodies | Rituxan

Campath | Rituxan | Rituxan Combos | Other Monoclonal Antibody (Mabs) for B- and T-cell NHL 

  Radiolabeled Antibodies

Monoclonal antibodies (Mabs) when administered in the body seek out and bind to cells in the body that have a specific protein (sometimes called a cluster of differentiation, or CD) It is thought that this binding activates the body's own defense mechanisms to attack these cells, and that the binding may also cause the cells to self-destruct. Targeting the attack on the cancer in this way reduces many of the side effects of broad-based chemotherapy treatments, which tend to damage more healthy tissues.

NOTE: ASCO.org links to abstracts 

Mab-apoptosis.jpg (24354 bytes) Signals that induce self-killing, and/or  mab-nk.jpg (38897 bytes) Immune Activation
 
Here are two illustrated ways that antibodies may kill tumors.  (Click images to enlarge.)
In the illustration, NK represents Natural Killer cells, but other effector cells can engage the antibody to induce killing, such as macrophages. 

Resources & News
ASH 2004 [3285]  In Vitro and In Vivo Anti-Lymphoma Activity of the Anti-HLA-DR Monoclonal Antibody 1D09C3. 
Session Type: Poster Session 555-III  abstracts2view
Anti-HLA-DR  PowerPoint Presentation
Anti-CD74 antibody - internalizing properties  prnews | PubMed | Related articles
 
In yet another presentation, Immunomedics' scientists showed that this *rapidly internalizing CD74 antibody* 
was very effective in killing human NHL cells in culture and NHL tumors growing in mice when the 
antibody is conjugated with the anticancer drug, doxorubicin. Dr. Horak commented: "Unexpectedly high 
efficacy in this preclinical model was found with a single injection of this antibody-drug conjugate, even in 
advanced disease." 
Webcast - Antibody Therapy for Non-Hodgkin’s Lymphomas - Dr Oliver Press  Moffitt Cancer Net
Off-Label Uses of Monoclonal Antibodies for Treatment of B-Cell Lymphoid or
Myeloid Malignancies http://www.bcbs.com/tec/Vol16/16_07.pdf  
Types & Combinations
Abstracts & Links
Rituxan (Rituximab) 

Treatment of cd20 positive b-cell lymphomas

 
See Details  FDA approved
Both normal and malignant cells express CD20. However, because precursor b-cells do not, normal b-cells will return  ~6 mo. after treatment.
Rituxan Combinations
The goal of combining combining antibodies, biologic or chemotherapy agents with Rituxan is to improve the response rate, and the duration of response.  
Other Combinations
Viragen Antibody Enhances Effect of Leading Cancer Drug   prnewswire | bloodjournal.org 
In Vitro study shows benefit of anti-CD55 antibody and Rituxan®
Preclinical: Fully human anti-MHC class II monoclonal antibody, 1D09C3, may have potent synergistic activity with Rituxan  press release
Dipeptidyl peptidase inhibitor and Rituxan  (PT-100)  ASCO
Rituxan + Antisense

Antisense is kind of gene therapy that down regulates Bcl-2, a protein that prevents cell death. This protein is overexpressed on many B-cell lymphomas.

 

TOPIC SEARCH  ASCO | PubMed 

Abstracts & Links
Investigational. It's hoped that these two agents in combination will help to overcome resistance to chemotherapy. One study opening soon (~Aug-02) adds this combination to CHOP for Mantle Cell lymphomas. See New York Weill Cornell Medical Center - call for details; the study is not posted on their Website yet.
Rituxan + chemotherapy

For CD20 positive b-cell indolent, transformed or aggressive lymphomas

TOPIC SEARCH  ASCO | ClinicalTrials.gov | PubMed 

Abstracts & Links
Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. Expert Rev Anticancer Ther. 2001 Aug;1(2):177-86. Review.
PMID: 12113023  PubMed
Immunochemotherapy in indolent non-Hodgkin's lymphoma.
Semin Oncol. 2002 Apr;29(2 Suppl 6):11-7. Review.
PMID: 12040529  PubMed
 
Rituxan + CpG 7909

CpG is a biological response modifier.

 

TOPIC SEARCH  ASCO | PubMed

"... immunostimulatory CpG ODN can enhance antibody dependent cellular cytotoxicity and warrant further evaluation as potential immunotherapeutic reagents in cancer."[1]

Abstracts & Links
  1. Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma. Blood. 1997 Apr 15;89(8):2994-8. PMID: 9108420
 
Rituxan + GM-CSF (Leukine)

GM-CSF stands for Granulocyte -Macrophage Colony-Stimulating Factor. It's a biologic that stimulates immunity, and possibly the expression of CD20 on B-cells.

 TOPIC SEARCH  ASCO | ClinicalTrials.gov | PubMed 
Abstracts & Links
Treatment of relapsed B-cell non-Hodgkin's lymphoma with a combination of  rituxan and G-CSF: final report on safety and efficacy. Leukemia. 2003 Aug;17(8):1658-1664. PMID: 12886256  PubMed | Related abstracts
Effect of GM-CSF, G-CSF or Methylprednisolone (MP) on Rituximab-Associated Complement-Mediated Cytotoxicity (CMC) on Non-Hodgkin’s Lymphoma (NHL) Cell Lines  ASCO 2001 # 1095
Mechanisms of G-CSF- or GM-CSF-stimulated tumor cell killing by Fc receptor-directed bispecific antibodies. J Immunol Methods. 2001 Feb 1;248(1-2):103-11. PMID: 11223072  PubMed
Beyond immunochemotherapy: combinations of rituximab with cytokines interferon-alpha2a and granulocyte-macrophage colony stimulating factor. Semin Oncol. 2002 Apr;29(2 Suppl 6):7-10. Review. PMID: 12040528  PubMed
 
Rituxan + Epratuzumab

Epratuzumab targets the CD22 antibody on B-cells

 

TOPIC SEARCH ASCO | ClinicalTrials.gov | PubMed 
Abstracts & Links
Epratuzumab (anti-CD22) and rituximab (anti-CD20) combination immunotherapy for non-Hodgkin's lymphoma: preliminary response data Year: 2002 Abstract No: 1060
Immunotherapy of non-Hodgkin's lymphoma with hLL2 (epratuzumab, an anti-CD22 monoclonal antibody) and Hu1D10 (apolizumab). Semin Oncol. 2002 Feb;29(1 Suppl 2):81-6. Review. PMID: 11842393  PubMed
 
Rituxan + Galiximab (anti-cd80)
 
A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with Rituxan for relapsed or refractory, follicular lymphoma. Ann Oncol. 2007 Jul;18(7):1216-23. Epub 2007 Apr 29. PMID: 17470451 

73 patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months.

 
Rituxan + interferon-alpha2a (IFN)

INF-alpha is a biological response modifier. 

NOTE: The pegylated version might reduce side effects and provide more consistent dosing.

 

TOPIC SEARCH  ASCO | ClinicalTrials.gov | PubMed 

Abstracts & Links
Beyond immunochemotherapy: combinations of rituximab with cytokines interferon-alpha2a and granulocyte-macrophage colony stimulating factor. Semin Oncol. 2002 Apr;29(2 Suppl 6):7-10. Review.
PMID: 12040528  PubMed
Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and Rituximab in patients with relapsed low grade non-Hodgkin's lymphoma. Haematologica. 2001 Sep;86(9):951-8. PMID: 11532623  PubMed
Combination immunotherapy of relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma with rituximab and interferon-alpha-2a.
Clin Cancer Res. 2000 Jul;6(7):2644-52. PMID: 10914705  PubMed
 
Rituxan + Interleukin-2 (IL-2)

IL-2, a cytokine, is a biological response modifier. (Proleukin®)   

NOTE: The pegylated version might reduce side effects and provide more consistent dosing.

TOPIC SEARCH  ASCO | ClinicalTrials.gov | PubMed 

Abstracts & Links
Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin's lymphoma.
Br J Haematol. 2002 Jun;117(4):828-34. PMID: 12060117  PubMed
Rituximab Plus Interleukin-2 in Treating Patients With Hematologic Cancer  ClinicalTrials.gov
Rituxan + Interleukin-11 (IL-11)

IL-11, a cytokine, is a biological response modifier.

 

TOPIC SEARCH  ASCO | ClinicalTrials.gov | PubMed 
Abstracts & Links
Monoclonal Antibody Therapy Plus Sargramostim and Interleukin-11 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma ClinicalTrials.gov
 
Rituxan + Interleukin-12 (IL-12)

IL-12, a cytokine, is a biological response modifier.

TOPIC SEARCH  ASCO | ClinicalTrials.gov | PubMed 

Abstracts & Links
Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin's lymphoma. Br J Haematol. 2002 Jun;117(4):828-34. PMID: 12060117  PubMed

 
Rituxan + Revlimid (Lenaliomide)
Study: Rituxan and/or Lenalidomide (Revlimid)
 
Condition: follicular lymphoma - relapsed following Rituxan-based combination therapy

Rationale and goal:  Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. 

Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Giving rituximab together with lenalidomide may kill more cancer cells.
TOPIC SEARCH: Mechanisms PubMed 
Outcome ASCO | Medscape | PubMed
Safety ASCO | PubMed 
Rituxan + Steroids

Steroids may complement Rituxan.

 

TOPIC SEARCH  ASCO | ClinicalTrials.gov | PubMed 

Abstracts & Links
Glucocorticoids and rituximab in vitro: synergistic direct antiproliferative and apoptotic effects. Blood. 2002 Sep 1;100(5):1765-73.
PMID: 12176898  PubMed 
Effect of GM-CSF, G-CSF or Methylprednisolone (MP) on Rituximab-Associated Complement-Mediated Cytotoxicity (CMC) on Non-Hodgkin’s Lymphoma (NHL) Cell Lines  ASCO 2001 # 1095

Other Antibodies for B- and T- Cell Lymphomas
Also See Pipeline
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Anti-cd69

Preclinical (early)

 Anti-cd69 ASCO | PubMed

"The leukocyte activation marker CD69 is a novel regulator of the immune response, modulating the production of cytokines including transforming growth factor-beta (TGF-beta)." PMID: 15692061

Abstracts and Resources

Induction of tumor NK-cell immunity by anti-CD69 antibody therapy. Blood. 2005 Jun 1;105(11):4399-406. Epub 2005 Feb 3. PMID: 15692061
 
Campath (alemtuzumab) 

 For CD52 positive B- and T-cell  lymphomas

Conditions: Small cell lymphocytic non-Hodgkin's lymphomas (NHL) of B- and T-cell type

 

CAMPATH ASCO | ASH | Medscape | ClinicalTrials.gov

"A humanized monoclonal antibody directed against the CD52 antigen with promising therapeutic effects in patients with small cell lymphocytic non-Hodgkin's lymphomas (NHL) of B- and T-cell type." [1]

Abstracts & Resources

Related PubMed Abstracts

  1. Monoclonal antibody therapy with CAMPATH-1H in patients with relapsed high- and low-grade non-Hodgkin's lymphomas: a multicenter phase I/II study. Ann Hematol. 2002 Jan;81(1):26-32. PMID: 11807632  PubMed
  2. Alemtuzumab in relapsed or refractory chronic lymphocytic leukemia and prolymphocytic leukemia. Leuk Lymphoma. 2002 May;43(5):1007-11.
    PMID: 12148879  PubMed
  3. Alemtuzumab in T-cell malignancies.
    Med Oncol. 2002;19 Suppl:S27-32. PMID: 12180489  PubMed
About  FDA.gov
Phase II study of alemtuzumab in chronic lymphoproliferative disorders.
Cancer. 2003 Aug 15;98(4):773-8. PMID: 12910522 | Abstracts
Campath  - alone or combined with Rituxan for refractory CLL  mdanderson.org
Campath data for CLL  abstracts

 
CT-011 antibody  


targets B7 family-associated protein,		 ClinicalTrials.gov

Indication: Lymphomas 

 
hA20
Humanized anti-CD20 antibody
  

Clinical Trials 

"According to Dr. Morschhauser, "These results with hA20 compare favorably to a published report of a similar patient population retreated with rituximab after at least one prior course of this antibody, where overall and complete response rates of 40% and 11%, respectively, were observed for the usual dose of 375 mg/m(2) weekly for four weeks (TA Davis et al., J Clin Oncol 2000; 18:3135-43).

Throughout the doses studied with hA20, an encouragingly high complete response rate, averaging 22%, and durable responses at each dose level were observed in these low-grade or follicular lymphoma patients." 
HUMAX-CD4 

For CD4 positive T-cell NHL

 

 Genmab's Enmab’S HUMAX-CD4 to be Tested in Cancer Patients

HuMax-CD4® is a high-affinity, fully human antibody that targets the CD4 receptor on T-cells and is currently in development for cutaneous T-cell lymphoma (CTCL) and non-cutaneous T-cell lymphoma (NCTCL). HuMax-CD4 has been designated a Fast Track Product by the US Food and Drug Administration (FDA), covering patients with CTCL who have failed currently available therapy. HuMax-CD4 has also been granted Orphan Drug status in the US,  Europe and Australia for the treatment of CTCL and for the treatment of NCTCL in Europe.  GENMAB
 
HuMax-CD4(TM) Continues to Show Long Lasting Responses in T-Cell Lymphoma Patients  prnewswire.com 
HUMAX-CD20 

For CD20 positive B-cell NHL

 

 "HuMax-CD20® is a fully human, high-affinity antibody targeted at the CD20 molecule in the cell membrane of B-cells .....  HuMax-CD20 is in clinical development for the treatment of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA) and diffuse large B-cell lymphoma (DLBCL). HuMax-CD20 has been designated a Fast Track Product by the FDA covering patients with CLL who have failed fludarabine therapy, including those who are refractory to available treatment. Genmab and GSK have announced details of a planned Phase II study in remitting relapsing multiple sclerosis (RRMS), expected to begin in 2008.  In addition, randomized Phase III studies in CLL and follicular NHL are being planned.  Other potential indications for HuMax-CD20 include Crohn's disease, Wegener's Granulomatosis, other B-cell lymphomas, including mantle cell lymphoma and autoimmune disease.."  genmab.com
Bispecific antibodies (BsAb) BiTE

For CD19 positive B-cell NHL   

Conditions: NHL

Animations

What is a BiTE™s?
micromet

How does it work?
 micromet   

 

"Bispecific monoclonal antibodies, with a dual specificity for tumor associated antigens on target cells and for surface markers on immune effector cells, have been shown (in vitro) to be effective in directing and triggering effector cells to kill target cells resulting in target cell lysis." [1]

Clinical Trials of Bispecific Antibodies

 

TOPIC SEARCH: Mechanisms PubMed 
Outcome ASCO | Medscape | PubMed
Safety ASCO | PubMed 

 

Abstracts & Links 
Related PubMed Abstracts 
  1. Performance of CD3xCD19 bispecific monoclonal antibodies in B cell malignancy. Leuk Lymphoma. 1995 Nov;19(5-6):381-93. Review.
    PMID: 8590837  PubMed
  2. Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer. 2002 Aug 20;100(6):690-7. PMID: 12209608  PubMed
  3. The Bi-Specific T-Cell Enhancer (BiTE) MT103 (MEDI-538) Induces Clinical Responses in Heavily Pre-Treated NHL Patients: Update from the Ongoing Phase I Study MT103-104.  ASH 2006
 
BL22

For CD22 positive B-cell lymphomas

BL22 recombinant immunotoxin BL22 

Conditions: NHL

 

BL22 TOPIC SEARCH: ASCO | ClinicalTrials.gov | PubMed | Web 

A toxin fused to an antibody that seeks and binds to receptors on lymphoma cells (Recombinant immunotoxins for the treatment of haematological malignancies)

Abstracts & Links 
Encouraging report on use of BL22 for Hairy cell Leukemia  cancerconsultants
Recombinant immunotoxins for the treatment of haematological malignancies. Expert Opin Biol Ther. 2004 Jul;4(7):1115-28. PMID: 15268678
Technology evaluation: BL22, NCI. Curr Opin Mol Ther. 2002 Feb;4(1):72-5. PMID: 11883697  PubMed
 
Eprituzamab (hLL2)

For CD22 positive B-cell NHL

Conditions: NHL

 

Current clinical investigations with humanized anti-CD22 includes as a treatment as single agent, in combination with Rituxan, and a radiolabeled version. 

Abstracts & Links

Related PubMed Abstracts

131I-labelled anti-CD22 MAb (LL2) in patients with B-cell lymphomas failing chemotherapy. Treatment outcome, haematological toxicity and bone marrow absorbed dose estimates. Acta Oncol. 2002;41(3):297-303.
PMID: 12195750  PubMed
Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents: a new generation of therapeutics. 
Leuk Lymphoma. 2002 May;43(5):953-9. PMID: 12148905  PubMed
Epratuzumab (anti-CD22) and rituximab (anti-CD20) combination immunotherapy for non-Hodgkin's lymphoma: preliminary response data Year: 2002 Abstract No: 1060
 
HeFi-1

For CD30 positive T-cell lymphomas

Condition: Refractory Anaplastic Large Cell Lymphoma

Clinical trials

 

 

Abstracts & Links
  1. Distinct effects of CD30 and Fas signaling in cutaneous anaplastic lymphomas: a possible mechanism for disease progression.
    J Invest Dermatol. 2000 Dec;115(6):1034-40.
    PMID: 11121138  PubMed
Hu1D10

For 1D10 positive B-cell lymphomas

Conditions:  NHL/CLL/SLL/MZL

Clinical Trials

 

Abstracts & Links
HLA TYPE: Recombinant IgA antibodies against HLA class II: a novel immunotherapeutic approach against B cell lymphoma Year: 2002 Abstract No: 1877
LMB-2 - Anti-Tac(Fv)-PE38

Recombinant immunotoxin (IL2R alpha+)

For Tac-expressing B- and T-cell NHL

Conditions: T-cell leukemia, B-cell NHL, CLL, cutaneous, peripheral and other T-cell lymphomas

Clinical Trials

             

 

Abstracts & Links
Anti-Tac Clinical Studies   ClinicalTrials.gov 
The anti-CD25 recombinant immunotoxin LMB-2 shows antitumor activity in patients with cutaneous T-cell lymphoma. Year: 2002 Abstract No: 33

 
Mono-dgA-RFB4

For CD22 positive B-cell NHL

Mono-dgA-RFB4 is a component of IMTOX 22

 
Abstracts & Links
Clinical Studies  ClinicalTrials.gov
 
IDEC114-20

For cd80 positive B-cell lymphomas

Conditions: NHL

Clinical Trials

Abstracts & Links
Clinical study  anti-cd80  
Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma. J Biol Chem. 2002 Mar 8;277(10):7766-75. PMID: 11726649  PubMed
 
Bevacizumab 

anti-VEGF - (tumor vascular endothelial growth factor)

Conditions: Aggressive NHL

Clinical Trials
Abstracts & Links
Clinical study listings for NHL  ClinicalTrials.gov 
The emerging role of angiogenesis inhibitors in hematologic malignancies. Oncology (Huntingt). 2002 May;16(5 Suppl 4):23-9.
PMID: 12102577  PubMed
 
Radiolabeled Antibodies