Description

Indication: Lymphomas, b-cell (expressing CD20)
 
AME-133v is hypothesized to result in an anti-CD20 therapy with greater potency and efficacy in all patients, but particularly in genetically defined subpopulations that respond poorly to rituximab (Rituxan)  because they express a low affinity version of the Fc receptor on their immune effector cells. A monoclonal antibody that has increased binding for this receptor should be more effective in stimulating effector cell killing and thus improve response to the antibody. This study is designed to provide evidence of the safety and a preliminary understanding of the efficacy of AME 133v

targets PD-1
(Programmed Death-1), an inhibitory receptor 

Compared to existing CD20 antibodies GA101 represents a novel, third generation antibody with significantly enhanced efficacy in a variety of in vitro and in vivo preclinical models. GA101 constitutes the first type II CD20 antibody successfully engineered for increased ADCC. Based on these data, GA101 is a promising therapeutic antibody candidate for the treatment of B-cell malignancies.  ASH 2007 and ASH 2007

Overview of technology by sponsor: PDF 

Targets cd70

 
Indication: Lymphomas and CLL

Cellular expression: Activated T and B cells, and macrophages

"MDX-1411 is a fully human monoclonal antibody that targets the CD70 receptor, which is a member of the tumor necrosis factor (TNF) family. CD70 is expressed in a number of cancers, including ccRCC primary tumors and metastatic lesions.

Preclinical in vitro studies showed that MDX-1411 binds to CD70 positive cells and induces antibody-dependent cellular cytotoxicity (ADCC), an important mechanism of action of therapeutic antibodies that induces the destruction of targeted cells by the immune system. Preclinical in vivo studies conducted in ccRCC xenograft models demonstrated anti-tumor activity. "  

Immunomedics Patents Internalizing Anti-CD74 Antibodies  Reuters 

 
Indication: Lymphomas 

CAT-8015 is an optimized version of  CAT-3888 with increased affinity for CD22. CD22 is a cell surface receptor expressed in a wide variety of B-cell malignancies. The anti-CD22 immunotoxin CAT-8015 comprises a dsFv that targets the CD22 receptor, fused with a specifically engineered toxin molecule that minimizes non-targeted toxicity, resulting in a highly specific, highly potent therapeutic molecule. The molecule acts by releasing the toxin intracellularly, after the whole immunotoxin has been internalised via the CD22 receptor.
" 

Indication: Lymphomas, b-cell 

Scant background information so far; one trial

Indication: Lymphomas, b-cell - expressing cd19

SAR3419 is an immunoconjugate consisting of an anti-CD19 monoclonal antibody conjugated to the maytansinoid DM4, a derivative of the cytotoxic agent maytansine (DM1), with potential antineoplastic activity. Anti-CD19-DM4 conjugate SAR3419 targets the cell surface antigen CD19, found on a number of B-cell-derived cancers. Upon antibody/antigen binding and internalization, the immunoconjugate releases DM4, which binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of CD19-expressing tumor cells. http://www.cancer.gov/ 

Intravenous Bispecific Antibody (4G7XH22) 

 
Indication: Lymphomas expressing CD22
 
"radioimmunotherapy (RAIT) using epratuzumab to deliver toxic radiation directly to lymphoma cells in small fractions." Source

APPROVED for relapsed indolent lymphoma. See Bexxar

Indication: Lymphomas, b-cell (expressing CD20) 
 
(iodine I 131 tositumomab)

Systematic Review: 

Indication: MDS
 
"The therapy involves infusing donor T lymphocytes engineered with a gene encoding an inactive apoptosis protein."

In immunology, APO866 exerts inhibitory effect on T-cells offering the potential as a treatment for autoimmune diseases " - Source

 ... AT-101 induces apoptosis in primary leukemia cells from patients with CLL. This effect is concentration dependent (IC50= 2μM) and it is independent of the expression of prognostic factors such as ZAP-70 or IgVH gene mutational status in the leukemia cells.

- AT-101 seems to have stronger pan-specific binding affinity for Bcl-2 family proteins than racemic gossypol, in particular to Mcl-1 and Bcl-XL. "

Background article PDF

 Source | See also CLLtopics overview

 Source  

The inhibition of the antiapoptotic Bcl-2 proteins is an attractive strategy for either restoring normal apoptotic process in cancer cells or making these cells more susceptible to conventional chemotherapy.  Source

 
Indication: Lymphoma, follicular
 
"CpG oligodeoxynucleotides (CpG-ODNs) affect innate and adaptive immune responses, including antigen presentation, costimulatory molecule expression, dendritic cell maturation, and induction of cytokines enhancing antibody-dependent cell-mediated cytotoxicity (ADCC)" Source

Indication: Lymphoma, cutaneous b- or t-cell
 
TG1042 is a third-generation, nonreplicating human adenovirus vector containing a human IFN-gamma cDNA insert." Source
Data: http://www.biovalley.com/images_messages/image2/749.pdf 

CPG-7909 (PF-3512676, ProMune^®): toll-like receptor-9 agonist in cancer therapy  expertopin.com 

Stimulation of toll-like receptor (TLR)9 activates human plasmacytoid dendritic cells and B cells, and induces potent innate immune responses in preclinical tumor models and in patients. CpG oligodeoxynucleotides (ODNs) are TLR9 agonists that show promising results as vaccine adjuvants and in the treatment of cancers, infections, asthma and allergy.

Phase I of AR-12, a PDK-1 Inhibitor Targeting the PI3K/Akt Pathway   http://bit.ly/13CT7p  

Sponsor: "AR-12 is potentially a first-in-class, orally available, PDK-1 (pyruvate dehydrogenase kinase isozyme 1) inhibitor that targets the PI3-K/Akt ocogenic pathway and also induces autophagy and the endoplasmic reticulum mediated apoptosis stress pathway."

Indication: Lymphomas
 
Novel anti-sense "The inactivation of MYC may be a specific and effective treatment for these tumors. To address for this possibility, I have developed a novel mouse model system to conditionally regulate MYC expression in mouse lymphocytes. Previously, I have used this model system to demonstrate that the inactivation of MYC can be sufficient to cause the sustained regression of cancers." Source

Indication: Lymphomas
 
NBAY 43-9006 is a "targeted drug" specifically engineered to inhibit something called the RAF kinase within the cancer cells. RAF in turn is part of the RAS oncogene pathway. RAS is a gene which drives cell division and is overexpressed in many cancers, including RCC. Source

Indication: Lymphoma, t-cell cutaneous
 
(Forodesine) PNP-inhibitor. May stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I/II trial to study the effectiveness BCX-1777 in treating patients who have refractory cutaneous T-cell lymphoma.

ASH: Forodesine HCl active single oral agent for advanced refractory CTCL abstracts2view.com

CS-1008 (humanized anti-DR5 antibody)

An Oral Inhibitor of Syk (Fostamatinib Disodium (FosD), Is Well-Tolerated and Has Significant Clinical Activity in DLBCL and SLL/CLL

http://ash.confex.com/ash/2008/webprogram/Paper5094.html 

n = 68 pts with relapsed/ refractory NHL in 3 separate disease cohorts: DLBCL (23); FL (21) and other B-cell NHL (24) including SLL/CLL (11), MCL (9) marginal zone/MALT (3) and lymphoplasmacytic NHL (1).  Median age was 61 (range 41-87); with  median of 5 prior therapies, including ASCT (16; 12 with DLBCL) and radioimmunotherapy (8). 

We conclude that disrupting BCR-induced signaling by inhibiting SYK kinase represents a safe and well-tolerated novel therapeutic approach to NHL.  In addition to significant responses in DLBCL and CLL/SLL, prolonged stable disease was observed in pts with FL.  FosD should be developed further, as a single agent and in rational combinations, for BCR-dependent B-cell NHLs.

"R788/R406 is a novel syk kinase inhibitor that blocks the activation of mast cells, B-cells and macrophages by blocking IgG signaling.

In this study, researchers at the Dana-Farber Cancer Institute and Brigham and Women's Hospital, in conjunction with researchers at Rigel, showed that R406 inhibited proliferation and was cytotoxic in multiple diffuse large B-cell lymphoma cell lines, confirming that R406/R788 may be useful in the treatment of certain B-cell lymphomas." Source

Bendamustine (Treanda) is effective in relapsed or refractory aggressive non-Hodgkin’s lymphoma  cancerconsultants.com

  Recently approved for CLL ... will likely be available off-label for other lymphomas based on strong supporting data.  

Treanda (Bendamustine) Full Prescribing information: FDA as PDF file

cyotoxic
inhibits DNA enzyme

 
Indication: Lymphomas
 
Bevacizumab is a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF-A). Source

 
Indication: Lymphomas, t-cell / GVHD
 
"Alefacept (well tolerated in treating psoriasis) reduced the number of CD4(+) and CD8(+) T cells, with selectivity for the memory subsets"   

Alefacept is well tolerated in patients with chronic plaque psoriasis.
J Cutan Med Surg. 2004 Dec;8 Suppl 2:14-9. Review.
PMID: 15668751
 

In Situ Tumor Ablation Creates an Antigen Source for the Generation of Antitumor Immunity  aacrjournals.org