Beta‐glucan enhanced killing of renal cell carcinoma micrometastases by monoclonal antibody G250 directed complement activation

Sier, Cornelis F.M.; Gelderman, Kyra A.; Prins, Frans A.; Gorter, Arko

doi:10.1002/ijc.20029

Cited by 39 publications

(18 citation statements)

References 47 publications

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“…These proteins can protect both normal and tumor cells from lysis mediated by the complement system. Bispecific mAbs that are antagonists for mCRPs and tumor antigen are therefore being developed (141)(142)(143).…”

Section: Interaction Of Igg With the Complement System: The Enhancemementioning

confidence: 99%

Engineering therapeutic monoclonal antibodies

Liu

Pop

Vitetta

2008

Immunological Reviews

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During last two decades, the chimerization and humanization of monoclonal antibodies (mAbs) have led to the approval of several for the treatment of cancer, autoimmune diseases, and transplant rejection. Additional approaches have been used to further improve their in vivo activity. These include combining them with other modalities such as chemotherapy and redesigning them for improved pharmacokinetics, effector function, and signaling activity. The latter has taken advantage of new insights emerging from an increased understanding of the cellular and molecular mechanisms that are involved in the interaction of immunoglobulin G with Fc receptors and complement as well as the negative signaling resulting from the hypercrosslinking of their target antigens. Hence, mAbs have been redesigned to include mutations in their Fc portions, thereby endowing them with enhanced or decreased effector functions and more desirable pharmacokinetic properties. Their valency has been increased to decrease their dissociation rate from cells and enhance their ability to induce apoptosis and cell cycle arrest. In this review we discuss these redesigned mAbs and current data concerning their evaluation both in vitro and in vivo.

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Section: Interaction Of Igg With the Complement System: The Enhancemementioning

confidence: 99%

Engineering therapeutic monoclonal antibodies

Liu

Pop

Vitetta

2008

Immunological Reviews

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“…Thus, the overexpression of mCRP plays a certain role in the evasion of the lung carcinoma cells against complement-mediated damage. Overexpression of mCRPs has been described in many tumors as well as in tumor cell lines from different origins, such as, renal cell carcinoma (22), melanoma (23), tumors of the B lymphoma (24) and ovarian carcinoma (25). Despite the apparent suitability of mAb for adjuvant immunotherapy of lung cancer, it is likely that the expression of intrinsic complement-regulators on tumor cells interfere with the potential cytotoxic effect of the antibody.…”

Section: Discussionmentioning

confidence: 99%

Neutralization of complement regulatory proteins CD55 and CD59 augments therapeutic effect of herceptin against lung carcinoma cells

Chen¹

2009

Oncol Rep

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Abstract. Human monoclonal anti-Her2/neu antibody (herceptin, also named trastuzumab) failed in the treatment of lung cancer when in combination with two chemotherapy agents gemcitabine and cisplatin, despite of its clinical benefit in women with Her2 positive breast cancer. The capacity of herceptin to activate human complement and complementdependent cytotoxicity against tumor cells was investigated in a study of tumor immunotherapy. We found that the expression of membrane complement regulatory proteins (mCRPs), CD55 and CD59 on non-small cell lung cancer (NSCLC) cells was closely correlated with histological types, prognosis and preoperational adjutant chemotherapy of the disease. Herceptin-mediated complement cytotoxicity to two human lung carcinoma cell lines exerted stronger killing effect on tumor cells after the neutralization of mCPRs via their antibodies. Furthermore, treatment of herceptin combined with chemo-agents had advantages over chemotherapy alone, while CD55 and CD59 expression levels both declined remarkably in A549 and H157 cell lines after incubation with IC 50 cisplatin for 72 h. Our data indicated that overexpression of mCRPs on tumor cells contributes to herceptin's acquisition of resistance to NSCLC, and its anticancer efficacy was enhanced when mCRPs were neutralized or cisplatin could be used to down-regulate their expression.

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“…Acceptance and utilization of BRMs, including CMG, is one of them. As β-D-glucan isolated from S. cerevisiae is water insoluble, has higher molecular weight, and is resistant against alkali-acid treatments, it was processed by carboxymethylation 15 on purpose to change these properties and facilitate its potential utilization in medicine. …”

Section: Discussionmentioning

confidence: 99%

The role of natural biopolymers in genotoxicity of mutagens/carcinogens elimination

Miadoková¹,

Svidová²,

Vlčková³

et al. 2005

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Nowadays naturally occuring compounds with the potential antimutagenic and anticarcinogenic effects are of great importance for their prospective use in cancer chemoprevention and treatment. The new water soluble derivative of microbial polysaccharide β-D-glucan-carboxymethyl glucan (CMG) belongs to such a category of natural substances. CMG isolated from the cell wall of baker's yeast Saccharomyces cerevisiae is included into the class of biopolymers known as biological response modifiers (BRMs) with a broad range of activities, above all ones interfering with cancer therapy. It was demonstrated on four experimental model systems that biological and consequential medicinal importance of CMG is based on the combined application with another active compound. In the Saccharomyces cerevisiae antimutagenicity assay CMG significantly reduced ofloxacin-induced mutagenicity in the yeast strain D7. CMG exerted bioprotective (anti-toxic and antimutagenic) effect after its simultaneos application with methyl methanesulphonate on the repair-deficient strain uvs10 of the unicellular green alga Chlamydomonas reinhardtii. In the Vicia sativa simultaneous phytotoxicity and anticlastogenicity assay CMG exerted statistically significant anticlastogenic efect against maleic hydrazide-induced clastogenicity in Vicia sativa L. Only in the Salmonella/microsome assay CMG did not exert statistically significant antigenotoxic effect, despite of the fact that it reduced 9-aminoacridine-induced mutagenicity in S. typhimurium TA97, but his + revertants decreasing was statistically significant only at the highest CMG concentration used. The data presented unambiguously documented that even biopolysaccharides (e.g., derivatives of β-glucan) belonging to the most abundant class of natural biopolymers may contribute to cancer prevention and therapy.

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Beta‐glucan enhanced killing of renal cell carcinoma micrometastases by monoclonal antibody G250 directed complement activation

Cited by 39 publications

References 47 publications

Engineering therapeutic monoclonal antibodies

Engineering therapeutic monoclonal antibodies

Neutralization of complement regulatory proteins CD55 and CD59 augments therapeutic effect of herceptin against lung carcinoma cells

The role of natural biopolymers in genotoxicity of mutagens/carcinogens elimination

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