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Agents that Target Disease Pathways > Antibodies (monoclonal) for Lymphomas

Last update: 01/02/2014

TOPICS
Campath | Rituxan | Rituxan Combination |
Other Monoclonal Antibody (Mabs) for B- and T-cell NHL |  Radiolabeled Antibodies

TOPIC SEARCH: PubMed: Monoclonal Antibodies | Rituxan

NEW: Antibody-based clinical trials  PAL

In the News:

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Antibodies - Medical News Today: Antibody Cancer Therapy Has A Bright Future
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Semin Hemat: Monoclonal Antibodies in Lymphoma –the First Decade
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Medical News Today: Antibody Cancer Therapy Has A Bright Future  

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. 

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

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2012 - Ofatumumab  - Chemoimmunotherapy with Ofatumumab in combination with CHOP in previously untreated follicular lymphoma onlinelibrary.wiley.com/
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brentuximab vedotin (drug / antibody conjugated antibody) - approved for Hodgkins lymphoma

FDA Briefing Document
Oncologic Drugs Advisory Committee Meeting
July 14, 2011 | BLA 125388
(Adcetris) brentuximab vedotin
Proposed Indication: Treatment of Relapsed or Refractory Hodgkin Lymphoma
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Novel antibodies in the treatment of lymphoma, S.A. Bhat, M.S. Czuczman  http://bit.ly/ccYZkg
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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
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Anti-HLA-DR  PowerPoint Presentation
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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." 
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Webcast - Antibody Therapy for Non-Hodgkin’s Lymphomas - Dr Oliver Press  Moffitt Cancer Net
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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
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Viragen Antibody Enhances Effect of Leading Cancer Drug   prnewswire | bloodjournal.org 
In Vitro study shows benefit of anti-CD55 antibody and Rituxan®
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Preclinical: Fully human anti-MHC class II monoclonal antibody, 1D09C3, may have potent synergistic activity with Rituxan  press release
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Dipeptidyl peptidase inhibitor and Rituxan  (PT-100)  ASCO

 

Rituxan + chemotherapy

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

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.

 

"... 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.

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

 

Abstracts & Links
 
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.

 

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.

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.

 

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.

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 


Other Antibodies for B- and T- Cell Lymphomas

Also See Pipeline
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Anti-cd69

Preclinical (early)

"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

 

"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

 

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
 
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HuMax-CD4(TM) Continues to Show Long Lasting Responses in T-Cell Lymphoma Patients  prnewswire.com 
Ofatumumab  cd20
(approved for refractory CLL) 

For CD20 positive B-cell NHL

 

bullet 2012 - Ofatumumab  - Chemoimmunotherapy with Ofatumumab in combination with CHOP in previously untreated follicular lymphoma onlinelibrary.wiley.com/

"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 
 

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

 

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
 
brentuximab vedotin
approved for Hodgkins lymphoma

FDA Briefing Document
Oncologic Drugs Advisory Committee Meeting
July 14, 2011 | BLA 125388
(Adcetris) brentuximab vedotin
Proposed Indication: Treatment of Relapsed or Refractory Hodgkin Lymphoma
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
 
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

Radiolabeled antibodies combine Monoclonal antibodies with radioactive agents. The goal of this combination is to bring additional killing power (radiation) to the malignant cells and fewer normal cells.

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Zevalin (IDEC-Y2B8)

Yttrium Y 90 ibritumomab tiuxetan  for CD20 positive B-cell lymphomas

 

 
Details Approved by the FDA

 

Bexxar

Iodine-131 Anti-B1 Antibody for CD20 positive B-cell lymphomas

 

 
Details Under review by FDA ODAC (Aug 2002)
Lym-1

Iodine I 131 monoclonal antibody for CD20 positive B-cell lymphomas

Condition: Recurrent NHL

 

Abstracts & Links
  • Milestones in the development of Lym-1 therapy.
    Hybridoma. 1999 Feb;18(1):1-11. Review.
    PMID: 10211782  PubMed
  • Increased survival associated with radiolabeled Lym-1 therapy for non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
    Cancer. 1997 Dec 15;80(12 Suppl):2706-11.
    PMID: 9406728  PubMed
Yttrium-90 Radiolabeled Humanized Anti-Tac and Calcium-DTPA

Condition: T-cell lymphoma

 

Abstracts & Links
  • Rapid and specific uptake of anti-Tac disulfide-stabilized Fv by interleukin-2 receptor-bearing tumors.
    Cancer Res. 1995 Jan 15;55(2):318-23.
    PMID: 7812965  PubMed
LR131 - Radiolabeled BLyS protein

For BLyS expressing B-cell lymphomas

Abstracts & Links
  • Radiolabeled BLyS protein (LR131) inhibits neoplastic B cell growth in vivo Year: 2002 Abstract No: 39
Other
Abstracts & Links
 

 

 
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