105Ad7 cancer vaccine stimulates anti-tumour helper and cytotoxic T-cell responses in colorectal cancer patients but repeated immunisations are required to maintain these responses

Durrant, Lindy G.; Buckley, D. J.; Robins, R. A.; Spendlove, Ian

doi:10.1002/(sici)1097-0215(20000101)85:1<87::aid-ijc16>3.0.co;2-k

Cited by 38 publications

(16 citation statements)

References 16 publications

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“…In contrast, patients in the phase I study could receive an immunization every 6 weeks until death, with most patients receiving between 3 and 7 vaccinations. Our recent studies have shown that with one exception patients do not appear to make a memory response to 105AD7 but show a brisk immune response following each immunization (Durrant et al 2000a) Thus the late stage of the colorectal cancer disease and the low number of injections may have contributed to the lack of survival benefit of 105AD7 in this trial. In addition over 50% of patients had significant tumour burdens, with disease in between 2 and 6 distinct sites.…”

Section: Discussionmentioning

confidence: 80%

“…Patients with primary colorectal cancer were immunized at diagnosis and then boosted post surgical resection. Results showed significant infiltration of helper T cells and natural killer cells (Durrant et al, 2000a(Durrant et al, , 2000b expressing the activation marker CD25 (Maxwell-Armstrong et al, 1999) at the tumour site relative to controls. This was associated with an increase in tumour cell apoptosis in trial patients (Amin et al, 2000).…”

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confidence: 99%

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Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer

et al. 2001

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Anti-idiotypic antibodies that bind at the active site of an antitumour antibody have the potential to act as surrogate antigens, thus stimulating immune responses against tumour antigens. 105AD7 is a human monoclonal anti-idiotypic antibody that was derived from a cancer patient (Austin et al, 1989) who had received radiolabelled 791T/36 antibody for diagnostic imaging of his colorectal cancer metastases. The 791T/36 antibody has recently been shown to bind to CD55 (Spendlove et al, 1999) a complement regulatory protein. This antigen is over-expressed by tumours presumably to protect them from complement-mediated lysis. 105AD7 has been shown to bind at the combining site of 791T/36 and can thus mimic CD55.A phase I clinical trial with 105AD7 precipitated on alum showed that anti-tumour T cell responses could be induced in advanced colorectal cancer patients with no associated toxicity. T cell responses included antigen-specific blastogenesis, enhanced serum IL-2 production (Robins et al, 1991) and activation of both helper and cytotoxic T cells (Durrant et al, 1999). Furthermore survival of these patients was impressive (12 months) in a patient population with extensive liver metastases. This was significantly longer than contemporary control patients . A second trial evaluated 105AD7 in the neoadjuvant setting. Patients with primary colorectal cancer were immunized at diagnosis and then boosted post surgical resection. Results showed significant infiltration of helper T cells and natural killer cells (Durrant et al, 2000a(Durrant et al, , 2000b expressing the activation marker CD25 (Maxwell-Armstrong et al, 1999) at the tumour site relative to controls. This was associated with an increase in tumour cell apoptosis in trial patients (Amin et al, 2000). Furthermore enhanced tumour killing by both natural killer cells and T cells has been seen following immunization with 105AD7 . The apparent survival benefit observed in the Phase I study was therefore evaluated in a double blind randomized trial of 105AD7 antibody precipitated on alum versus an alum control vaccination.

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Section: Discussionmentioning

confidence: 80%

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confidence: 99%

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer

et al. 2001

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“…It is well established in several systems that monoclonal anti-Id Abs could potentially have a role in vaccine development by virtue of their ability to mimic tumor Ags and stimulate the immune system (32)(33)(34)(35)(36)(37). Although Ab2 mAbs bearing the internal image of tumor-associated Ags are considered excellent candidates for immunotherapy, it has been demonstrated that the induction of Agspecific humoral response due to the immunization with ␤-type Ab2 is not predictive of the biological effect induced by the Ab (38,39).…”

Section: Discussionmentioning

confidence: 99%

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

Alfonso

Diaz

Hernández

et al. 2002

The Journal of Immunology

112

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We generated the 1E10 γ-type anti-idiotype mAb (Ab2) specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with Ags expressed on human melanoma and breast carcinoma cells. This Ab2 mAb induced an Ab response in animal models sharing immunochemically defined idiotopes with the Ab1. The treatment of tumor-bearing mice with 1E10 mAb induced a strong antitumor activity. A clinical trial was conducted in 20 patients with advanced malignant melanoma. Patients were treated with six intradermal injections of aluminum hydroxide-precipitated 1E10 anti-Id mAb given at 2-wk intervals. Sixteen of the 17 patients who received at least four doses of the anti-Id vaccine develop Ab3 Abs capable of inhibiting Ab2 binding to Ab1 (Ab3Id+). In contrast to the incapacity of 1E10 mAb to generate Ab3 Abs with the same antigenic specificity as the Ab1 mAb in mice, a very specific and strong Ab3 response against N-glycolyl-containing gangliosides was induced in 16 patients (Ab3Ag+). No evidence of serious or unexpected adverse effects has been observed in this clinical trial. 1E10 anti-Id vaccine was safe, well tolerated, and immunologically effective, with most patients being able to generate a specific immune response against 1E10 and Neu-glycolyl-GM3 ganglioside.

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“…This limits the use of antibody-mediated cell lysis and vaccination for therapy. For ADCC, high amounts of CD55 inactivate the complement, which is needed by the therapeutical antibodies (Riethmüller et al, 1994), and low expression reduces immunological processes (Durrant et al, 2000).…”

Section: Hensel Et Almentioning

confidence: 99%

“…Overexpression has been found in, eg, breast, colon, and stomach carcinoma (Hofman et al, 1994;Koretz et al, 1992;Niehans et al, 1996), and this overexpression makes CD55 a suitable target for cancer vaccines in the treatment of colon carcinoma (Spendlove et al, 1999). Vaccination with a human anti-idiotype antibody that mimics CD55 was used for adjuvant treatment of colon carcinoma and resulted in activation of a cellular anti-tumor response (Durrant et al, 1995(Durrant et al, , 2000. However, this overexpression of CD55 and other complement-inactivating molecules limits therapeutical approaches that depend on the help of complement, as in antibody-dependent cellular cytotoxicity (ADCC) (Gorter and Meri, 1999).…”

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confidence: 99%

Regulation of the New Coexpressed CD55 (Decay-Accelerating Factor) Receptor on Stomach Carcinoma Cells Involved in Antibody SC-1–Induced Apoptosis

Hensel

Hermann

Brändlein

et al. 2001

Laboratory Investigation

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SUMMARY:The human monoclonal antibody SC-1 was isolated from a patient with a diffuse-type adenocarcinoma of the stomach using somatic cell hybridization. The immunoglobulin (Ig)M antibody reacts specifically with diffuse-(70%) and intestinal-type (25%) gastric adenocarcinoma and induces apoptosis in vitro and in vivo. When used in clinical trials with stomach carcinoma patients, significant apoptotic and regressive effects in primary tumors have been observed with the antibody SC-1. The SC-1 receptor is a new 82 kd membrane-bound isoform of glycosylphosphatidylinositol (GPI)-linked CD55 (decayaccelerating factor, DAF). CD55 is known to protect cells from lysis through autologous complement and is coexpressed with the ubiquitously distributed 70 kd isoform. The SC-1-specific CD55 isoform is up-regulated shortly after antibody binding, followed by an internalization of the antibody/receptor-complex, whereas the membranous expression of wild-type CD55 remains unchanged. The apoptotic process is marked by cleavage of cytokeratin 18, indicating the involvement of caspase-6 in the apoptotic process. In contrast to other apoptotic pathways, a cleavage of poly(ADP-ribose)polymerase (PARP) is not observed. The expression of the cell-cycle regulator c-myc becomes up-regulated, whereas expression of topoisomerase II␣ is down-regulated. Induction of apoptosis leads to an increase in the internal Ca 2ϩ concentration, which is not necessary for the apoptotic process but for the transport of newly synthesized SC-1-specific CD55 isoform to the membrane. (Lab Invest 2001, 81:1553-1563.

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105Ad7 cancer vaccine stimulates anti-tumour helper and cytotoxic T-cell responses in colorectal cancer patients but repeated immunisations are required to maintain these responses

Cited by 38 publications

References 16 publications

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer

Randomized double-blind phase II survival study comparing immunization with the anti-idiotypic monoclonal antibody 105AD7 against placebo in advanced colorectal cancer

An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients

Regulation of the New Coexpressed CD55 (Decay-Accelerating Factor) Receptor on Stomach Carcinoma Cells Involved in Antibody SC-1–Induced Apoptosis

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