Enhancing the Effect of THERATOPE STn-KLH Cancer Vaccine in Patients with Metastatic Breast Cancer by Pretreatment with Low-Dose Intravenous Cyclophosphamide

MacLean, G D; Miles, D. W.; Rubens, R. D.; Reddish, Mark A.; Longenecker, B. M.

doi:10.1097/00002371-199607000-00006

Cited by 146 publications

(63 citation statements)

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“…We chose KLH for this purpose, since KLH has shown useful immunological properties (15,38). Alternatively, to avoid the detection of antibodies specific for KLH in ELISA, human serum album (HSA) was employed as the carrier protein of the capture reagents.…”

Section: Resultsmentioning

confidence: 99%

Improving the Antigenicity of sTn Antigen by Modification of Its Sialic Acid Residue for Development of Glycoconjugate Cancer Vaccines

Guo

2006

Bioconjugate Chem.

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Sialyl Tn (sTn) antigen is a sialylated disaccharide abundantly expressed by many tumors. To search for effective cancer immunotherapies based on sTn antigen, this work designed and synthesized a series of unnatural N-acyl derivatives of sTn and studied their immunological property. For this purpose, an efficient method was developed to synthesize the natural and unnatural forms of sTn antigen and their protein conjugates. The resultant glycoconjugates were used to immunize C57BL/ 6 mice, and the immune response was assessed by ELISA. Whereas the keyhole limpet hemocyanin (KLH) conjugate of sTn elicited low levels of IgM antibodies, the KLH conjugates of N-iso-butanoyl sTn and N-phenylacetyl sTn, especially the latter, induced high titers of antigen-specific IgG antibodies, showing a T-cell dependent response which is critical for the antitumor activity. The results suggest that the modified forms of sTn, especially N-phenylacetyl sTn, have improved antigenicity and promising immunological properties for being used as cancer vaccines.

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Section: Resultsmentioning

confidence: 99%

Improving the Antigenicity of sTn Antigen by Modification of Its Sialic Acid Residue for Development of Glycoconjugate Cancer Vaccines

Guo

2006

Bioconjugate Chem.

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“…The rationale for incorporating low-dose intravenous cyclophosphamide in the tecemotide schedule is based on a trial by MacLean and colleagues 17 that showed a superior immune response to the STn-KLH (Theratope) vaccine in patients with breast cancer with intravenous versus oral cyclophosphamide. Patients then received tecemotide (contract manufacturer: Baxter Pharmaceutical Solutions LLC, Bloomington, IN, USA) or placebo (appendix).…”

Section: Methodsmentioning

confidence: 99%

Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial

Butts¹,

Socinski²,

Mitchell

et al. 2014

The Lancet Oncology

456

331

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“…Although chemotherapeutic immunomodulation is not widely used in cancer vaccine trials, there is substantial preclinical and clinical evidence to suggest that Cyclophosphamide can augment the induction of antigen-specific immunity. 18,[23][24][25][26] Importantly, the trial also included a control group that received Cyclophosphamide and GM-CSF but no autologous hemoderivative. The vaccinated group had a higher frequency of stable (SD) or responding (PR) disease than did the control group (p < 0.001).…”

Section: A New Twist On Autologous Cancer Vaccinesmentioning

confidence: 99%

A New Twist on Autologous Cancer Vaccines

Emens¹

2003

Cancer Biology & Therapy

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Physicians have had a long-standing interest in marshalling the cancer patient's own immune system to effect tumor rejection. The use of cancer vaccines to activate an endogenous antitumor immune response has the advantages of exquisite tumor specificity, low toxicity, and potential durability due to the phenomenon of immunologic memory. Moreover, cancer vaccines are an attractive complement to the standard cancer treatment modalities of surgery, radiation therapy, and chemotherapy, offering a non-toxic treatment strategy that is likely to be non-cross resistant. Even with these advantages, the use of therapeutic cancer vaccines also poses significant challenges. Their efficacy is hampered by the extent of the tumor burden, relatively well entrenched mechanisms of tumor-specific immune tolerance, and the potential plasticity of the tumor cells themselves. From a practical point of view, the development of tumor vaccines is further limited by the technical limitations posed by the nature of the vaccination platform itself. In this issue of Cancer Biology & Therapy, Lasalvia-Prisco and colleagues report the results of the first clinical trial testing a novel vaccine formulation utilizing an autologous hemoderivative for the treatment of advanced solid malignancies. 1 While clearly preliminary, their approach is intriguing because it circumvents many of the practical obstacles to the development of effective vaccines for cancer therapy.Tumor vaccine formulations can be broadly divided into those that are well defined, and those that are. 2 Well-defined tumor vaccines contain known tumor antigens; examples include peptide-based, protein-based, and plasmid DNA vaccines. These vaccines offer the advantages of relative ease of manufacture, clear targets for the monitoring of immune responses to vaccination, and a good safety record to date. One disadvantage to the use of precisely targeted tumor vaccines is that many tumor antigens seem to activate antigenspecific immunity that is incapable of mediating a tumor rejection response. This concept is supported by the results of studies characterizing the natural and vaccine-induced immune responses in melanoma patients who continue to have disease progression despite the presence of antigen-specific tumor immunity. 2-7 A second disadvantage to highly targeted cancer immunotherapies is that they favor the selection of antigen loss variants, ultimately resulting in the outgrowth of a subpopulation of antigen-negative tumor cells that are by definition resistant to therapy. [8][9][10]

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Enhancing the Effect of THERATOPE STn-KLH Cancer Vaccine in Patients with Metastatic Breast Cancer by Pretreatment with Low-Dose Intravenous Cyclophosphamide

Cited by 146 publications

References 0 publications

Improving the Antigenicity of sTn Antigen by Modification of Its Sialic Acid Residue for Development of Glycoconjugate Cancer Vaccines

Improving the Antigenicity of sTn Antigen by Modification of Its Sialic Acid Residue for Development of Glycoconjugate Cancer Vaccines

Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial

A New Twist on Autologous Cancer Vaccines

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