‘Rituximab-induced inhibition of antiapoptotic cell survival pathways: implications in chemo/immunoresistance, rituximab unresponsiveness, prognostic and novel therapeutic interventions’

Bonavida, Benjamin

doi:10.1038/sj.onc.1210365

Cited by 182 publications

(158 citation statements)

References 40 publications

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“…Lymphoma cells may become resistant by decreased expression of CD20 antigen, or they may also activate antiapoptotic signal transduction pathways, which Immunotherapy of NHL with Bi20 and DLI R Buhmann et al renders these cells resistant to chemotherapy. 19,20 Host factors involve effector cells of antibody-dependent cellular cytotoxicity and the reticulo-endothelial system removing antibody-loaded cells. 18 These functions may be defective;…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Buhmann

Simões

Stanglmaier³

et al. 2008

Bone Marrow Transplant

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Donor lymphocyte infusions (DLIs) after allo-SCT displayed limited use in CLL and highly malignant nonHodgkin's lymphoma (NHL). Here we studied whether Bi20 (FBTA05), a novel trifunctional bispecific antibody targeting CD20 on lymphoma cells and CD3 on T cells, could induce GVL responses in combination with DLI or mobilized PBSCT after allogeneic transplantation in these diseases. Six patients (three cases with p53-mutated CLL and three with high-grade NHL (HG-NHL)) refractory to standard therapy were treated with escalating doses of Bi20 (range 10-2000 lg) followed by DLI or SCT. Thereby, all CLL patients showed a prompt but transient clinical and hematological response. In one patient with HG-NHL, we observed a halt in progression for almost 4 months. Side effects (fever, chills and bone pain) were tolerable and appeared at antibody dose levels between 40 and 200 lg. The cytokine profile was characterized by transient increases of IL-6, IL-8 and IL-10. Neither human anti-mouse antibodies nor GVHD developed, allowing repeated treatment courses. In summary, the trifunctional antibody Bi20 induced prompt antitumor responses in extensively pretreated, p53-mutated alemtuzumab and rituximab refractory patients indicating its therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Buhmann

Simões

Stanglmaier³

et al. 2008

Bone Marrow Transplant

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“…Rituximab regulates several signaling pathways that promote cell survival and proliferation, including the PI3K, nuclear-factor j-B (NF-kB), as well as the ERK signaling pathways [9]. We have previously shown that the proteasome inhibitor bortezomib specifically targets NF-kB in WM cells [10], and enhances the cytotoxic activity of rituximab in antibody-dependent cellular cytotoxicity assays [11].…”

Section: Introductionmentioning

confidence: 99%

Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia

et al. 2010

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This study aimed to determine the activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenströ m Macroglobulinemia (WM). Patients with no prior therapy and symptomatic disease were eligible. Patients received bortezomib IV weekly at 1.6 mg/m 2 on days 1, 8, 15, q 28 days 3 6 cycles, and rituximab 375 mg/m 2 weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response (MR). Twenty-six patients were treated. At least MR was observed in 23/26 patients (88%) (95% CI: 70-98%) with 1 complete response (4%), 1 near-complete response (4%), 15 partial remission (58%), and 6 MR (23%). Using IgM response evaluated by nephlometry, all 26 patients (100%) achieved at least MR or better. The median time to progression has not been reached, with an estimated 1-year event free rate of 79% (95% CI: 53, 91%). Common grade 3 and 4 therapy related adverse events included reversible neutropenia in 12%, anemia in 8%, and thrombocytopenia in 8%. No grade 3 or 4 neuropathy occurred. The combination of weekly bortezomib and rituximab exhibited significant activity and minimal neurological toxicity in patients with untreated WM. Am. J. Hematol. 85:670-674, 2010. V

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“…21,22 Despite these advances, ,50% of NHL patients are unresponsive to rituximab, 23 and some of the responsive patients develop resistance to further rituximab treatment. 24 Furthermore, CLL remains incurable with these therapies. Patients undergoing treatment inevitably relapse, become increasingly refractory to treatment, and often acquire high-risk chromosomal abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

You

et al. 2011

Cell Mol Immunol

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Many monoclonal antibodies (mAbs) have been extensively used in the clinic, such as rituximab to treat lymphoma. However, resistance and non-responsiveness to mAb treatment have been challenging for this line of therapy. Complement is one of the main mediators of antibody-based cancer therapy via the complement-dependent cytolysis (CDC) effect. CD59 plays a critical role in resistance to mAbs through the CDC effect. In this paper, we attempted to investigate whether the novel CD59 inhibitor, recombinant ILYd4, was effective in enhancing the rituximab-mediated CDC effect on rituximab-sensitive RL-7 lymphoma cells and rituximab-induced resistant RR51.2 cells. Meanwhile, the CDC effects, which were mediated by rituximab and anti-CD24 mAb, on the refractory multiple myeloma (MM) cell line ARH-77 and the solid tumor osteosarcoma cell line Saos-2, were respectively investigated. We found that rILYd4 rendered the refractory cells sensitive to the mAb-mediated CDC effect and that rILYd4 exhibited a synergistic effect with the mAb that resulted in tumor cells lysis. This effect on tumor cell lysis was apparent on both hematological tumors and solid tumors. Therefore, rILYd4 may serve as an adjuvant for mAb mediated-tumor immunotherapy. Keywords: CD59; complement; lymphoma; multiple myeloma; rituximab INTRODUCTIONMonoclonal antibody (mAb) therapy is becoming a powerful approach and is increasingly used in the clinic for the treatment of different types of cancer through targeting specific cancer antigens. Rituximab, the first mAb approved for cancer therapy by the Food and Drug Administration, has been successfully used in the treatment of B-cell non-Hodgkin's B-lymphoma (NHL) via specifically targeting the CD20 molecule on the B lymphocyte membrane. Treatment with rituximab has lead to greatly improved clinical outcomes. 1 Trastuzumab (Herceptin) is used to treat HER2-positive breast cancer. Other new mAbs are actively being developed. Once the antibodies (Abs) are given, they can then recruit other parts of the immune system to destroy the cancer cells or to enhance the immune response against the cancer. The mechanism of action of these Abs and the host and cellular factors that influence the immune response following Ab treatment are not completely known. The induction of apoptosis, Abdependent cell cytotoxicity and complement-mediated cell death (CDC) are the proposed mechanisms of action of these Abs. 2 Complement is one of the main mediators of Ab-based cancer therapy via the CDC effect. When cancer therapeutic Abs activate the so-called classical complement pathway, they trigger the formation of the membrane attack complex on cancer cells, leading to the killing of cancer cells through CDC. 3 CD59, a critical membrane complement regulator, inhibits membrane attack complex formation by binding to

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‘Rituximab-induced inhibition of antiapoptotic cell survival pathways: implications in chemo/immunoresistance, rituximab unresponsiveness, prognostic and novel therapeutic interventions’

Cited by 182 publications

References 40 publications

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia

Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

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