Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1–KLH and GD3–KLH conjugates

Kim, Soo Kie; Ragupathi, Govindaswami; Cappello, Sarah; Kagan, Ella; Livingston, Philip O.

doi:10.1016/s0264-410x(00)00195-x

Cited by 87 publications

(57 citation statements)

References 16 publications

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“…They possess certain adjuvant activities, due to their structural features of sugar chain(s), its length, and hydrophilic and lipophilic properties [236]. Therefore, their adjuvant activity can be further modified by structural modifications such as GPI-0100 [237]. The widely used saponin-based adjuvants are Quil A, isolated from the bark of Quillaja saponaria (QS) Molina, and QS21, a more purified form, is the 21st of 22 fractions in RP-HPLC trace of semipurified QS bark extracts [238].…”

Section: Saponins and Qs21mentioning

confidence: 99%

“…Yet, use of KLH conjugate alone may or may not initiate adequate immune response and another adjuvant often has to be used. Such combinations include KLH conjugates with QS21 for cancer antigen (GD3; ganglioside) [238], with Freund's adjuvant for influenza virus A M2 peptide [269], and with other adjuvants for cancer antigens (MUC1 and GD3) [237,244]. The structure of linkers between hapten/antigen and KLH carrier protein may have a significant effect on the immunogenicity and selectivity of the conjugated vaccine [270].…”

Section: Carrier Proteinsmentioning

confidence: 99%

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Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Saponins and Qs21mentioning

confidence: 99%

Section: Carrier Proteinsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…The saponin-based adjuvant GPI-0100 was obtained from Galenica (Birmingham, AL), and QS-21 was from Immunizations Unless otherwise specified, we followed a standard protocol that generates consistently high titers in mice by immunizing thrice at 2-week intervals on days 0, 14, and 28 with 35 Ag KLH-FITC admixed with 100 Ag GPI-0100 (or 20 Ag QS-21) as the adjuvant (this regimen represents a ''full'' vaccination, as noted herein). QS-21 is the natural adjuvant purified from the plant saponin, and its immunostimulatory property is similar to that of its semisynthetic analogue GPI-0100 (16,17). For evaluating the effect of antibody titer on the pharmacokinetics of 3 H-folate-FITC, mice were given full or partial immunizations as described in Fig.…”

Section: Methodsmentioning

confidence: 99%

Preclinical pharmacokinetics, tissue distribution, and antitumor activity of a folate-hapten conjugate–targeted immunotherapy in hapten-immunized mice

Parker

et al. 2006

Molecular Cancer Therapeutics

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Folic acid (pteroylglutamic acid) represents a useful ligand for targeted cancer therapies because it binds to a common epithelial tumor antigen known as the folate receptor. We previously devised an immunotherapy strategy that uses a bispecific ligand, a folate-hapten (FITC) conjugate, to redirect endogenously induced anti-FITC antibodies to folate receptor -positive tumor cells following parenteral administration. Here, we present results from preclinical pharmacokinetic and tissue biodistribution studies using a radioactive folate-FITC conjugate and results from dose optimization studies done in tumor-bearing animals. Folate-FITC was found to be rapidly eliminated in non-immunized mice; however, in immunized hosts, folate-FITC was shown to form immune complexes with FITC-specific antibodies, the consequence of which was a f173-fold increase in drug exposure (i.e., area under the curve). Using a newly developed ELISA assay, the extent of circulating anti-FITC antibodies occupied by parenterally given folate-FITC was determined to be proportional to the given dose. Furthermore, high doses of folate-FITC were found to promote the cosaturation of tumor cell surface folate receptors and circulating FITC-specific antibodies, blocking the immune recognition of tumor cells and thereby reducing antitumor activity. Nonetheless, by extending the duration of treatment and administering subsaturating doses of folate-FITC, enhanced antitumor response was observed in mice bearing established folate receptor -positive M109 tumors. Overall, results from the present study may help to guide clinicians through on-going clinical investigations of folate-targeted immunotherapy. [Mol Cancer Ther 2006;5(12):3258 -67]

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“…Combinations of immunostimulatory agents may be required to induce the most robust immune response. Preliminary preclinical studies of combinations suggest CpG ODN can contribute to enhancing immune responses more effectively than immune adjuvants currently being developed for clinical use (37). A recent finding of our own laboratory is the synergistic relationship between CpG ODN and another member of the IL-2 family of cytokines, interleukin 21 (IL-21).…”

Section: ) Cpg Odn and Vaccination Strategiesmentioning

confidence: 99%

CpG oligodeoxynucleotides as immunotherapy in cancer

Jahrsdörfer

Weiner

2008

Update on Cancer Therapeutics

123

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Preclinical and early clinical trials indicate synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG ODN) have potent immunostimulatory effects and can enhance the anticancer activity of a variety of cancer treatments. Synergy between CpG ODN and monoclonal antibodies has been noted in various preclinical models. Early clinical trials indicate CpG ODN and monoclonal antibodies can be administered safely together. Preclinical models indicate CpG ODN can enhance the anti-tumor activity of both chemotherapy and radiation therapy. Thus, one possible approach to the use of CpG ODN was to use it in combination with cytotoxic chemotherapy with the goal of enhancing presentation of tumor antigen from dying cancer cells. Promising results in a randomized phase II trial in patients with non-small cell lung cancer led to initiation of two large randomized phase III trials comparing CpG ODN plus chemotherapy to chemotherapy alone. Unfortunately, interim analysis of these trials indicated CpG ODN was unlikely to enhance efficacy of chemotherapy, and they were stopped. CpG ODN also holds promise as a component of cancer vaccines including those composed of protein antigen, peptides, whole tumor cells, and antigenpulsed dendritic cells. Finally, CpG ODN has been combined with a variety of cytokines to enhance NK activation, promote development of an active anti-tumor immune response or induce apoptosis of malignant cells that express the TLR9 receptor. Overall, both preclinical and early clinical trials suggest CpG ODN may be a valuable component of a variety of approaches to cancer therapy. However, clinical development of this recently discovered, novel class of immunostimulatory agents is just beginning, and we still have much to learn about the optimal approach to their use, and their potential.

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Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1–KLH and GD3–KLH conjugates

Cited by 87 publications

References 16 publications

Selection of Adjuvants for Enhanced Vaccine Potency

Selection of Adjuvants for Enhanced Vaccine Potency

Preclinical pharmacokinetics, tissue distribution, and antitumor activity of a folate-hapten conjugate–targeted immunotherapy in hapten-immunized mice

CpG oligodeoxynucleotides as immunotherapy in cancer

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