Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans

Davis, Ian D.; Chen, Weisan; Jackson, Heather; Parente, Phillip; Shackleton, Mark; Hopkins, Wendie; Chen, Qiyuan; Dimopoulos, Nektaria; Luke, Tina; Murphy, Roger; Scott, Andrew M.; Maraskovsky, Eugene; McArthur, Grant A.; MacGregor, Duncan; Sturrock, Sue; Tai, Tsin Yee; Green, Simon; Cuthbertson, Andrew G. S.; Maher, Darryl; Miloradovic, Lena; Mitchell, Susan V; Ritter, Gerd; Jungbluth, Achim A.; Chen, Yao Tseng; Gnjatic, Sacha; Hoffman, Eric W.; Old, Lloyd J.; Cebon, Jonathan

doi:10.1073/pnas.0403572101

Cited by 396 publications

(335 citation statements)

References 30 publications

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“…10 -12 3) Owing to its high immunogenicity and broad expression in a variety of cancers, NY-ESO-1 has been chosen as the prototype for analysis in a number of cancer vaccine trials. 13 Monitoring the antibody titers against NY-ESO-1 may serve at least 2 immediate purposes: as a criterion for enrollment into NY-ESO-1 specific vaccine trials and as a simple assay for assessing the immunologic and clinical responses of the treatment. In the future, simultaneous measurement of Ab responses against NY-ESO-1 and multiple other TAA may provide important information regarding cancer prognosis and progression.…”

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confidence: 99%

Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

Zeng

Aldridge

Wang

et al. 2004

Intl Journal of Cancer

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Monitoring the spontaneous antibody (Ab) response against a panel of relevant tumor-associated antigens (TAA) in cancer patients may provide useful information regarding the clinical status of cancer. However, current Ab detection approaches require the purification of recombinant proteins, which is often difficult to achieve. In order to bypass the purification of recombinant proteins, we identified a dominant B-cell epitope from a shared tumor antigen NY-ESO- In the last 10 years, molecular identification of TAA has clearly demonstrated that the human immune system can react with endogenously arising cancer cells. 1 . Both the cellular and humoral arms of the human immune system recognize autologous TAA derived from cancer cells. 2,3 Of particular interest to the serological analysis of human cancers is the identification of TAA recognized by antibodies (Ab) present in the sera of cancer patients. 4 SEREX, or the serological analysis of recombinant cDNA expression libraries of human cancers, has been the primary approach to identify TAA based on their recognition by Ab. Up to now, there are at least 1,800 TAA identified based on recognition by Ab present in patients' sera. 5 . These TAA include targets from many cancer types, such as melanoma, renal cancer, Hodgkin's disease, esophageal cancer, lung cancer, colon cancer, gastric cancer, breast cancer, prostate cancer and so on. 3 The discovery of these TAA provides molecular details of the humoral immune response to autologous tumors. More importantly, the discovery of these molecules awakens the old hope of finding serological markers for cancer detection, diagnosis and prognosis. However, most of the SEREX-defined antigens do not or only react with few allogeneic sera. To investigate Ab responses against a large panel of TAA that covers a wide spectrum of patients with a particular cancer requires the purification of individual TAA protein, which is expensive and difficult to achieve. To circumvent the requirement of purifying individual protein, we propose identifying dominant B-cell epitopes from TAA for detection of Ab against TAA. We choose NY-ESO-1 as a prototype for identifying B-cell epitopes for the following reasons: 1) NY-ESO-1 is a cancer/testis antigen, which is expressed in a number of human cancers including those of the esophageal, 6 prostate, head and neck, lung, ovarian, breast, neuroblastoma, 7 gastric, as well as melanoma, hepatocellular carcinoma (HCC), T cell lymphoma and sarcoma. 8 Approximately 20 -30% of the above-mentioned cancers express the protein, and moreover, nearly 40 -50% of the patients with NY-ESO-1 expressing tumors develop antibodies against the protein. 9 2) Ab titers against NY-ESO-1 are driven by antigen expression of the endogenously arising tumor, and several studies have suggested that Ab titers against NY-ESO-1 correlated with advanced stages of the antigen-positive tumor in melanoma, transitional cell carcinoma and prostate cancer. 10 -12 3) Owing to its high immunogenicity and broad expression in a variety of ca...

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confidence: 99%

Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

Zeng

Aldridge

Wang

et al. 2004

Intl Journal of Cancer

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“…The new adjuvant ISOMATRIX, a saponin-based adjuvant, which is known to induce strong antibody-and T cell responses upon vaccination, was used in a placebo controlled trial with the NY-ESO-1 protein (17). Using the RAYS technology and patient sera from this NY-ESO-1/ISCOMATRIX vaccine trial, we analyzed in detail the humoral responses against NY-ESO-1 and the highly homologous CTA LAGE-1A and LAGE-1B as well as other CTA such as SSX2, SSX4, CT-7 and CT-10 before and after vaccination.…”

Section: Introductionmentioning

confidence: 99%

Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad antibody responses in humans, a RAYS-based analysis

et al. 2011

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Abstract. Antibody responses to tumor antigens play an important role in initiating a cellular antitumor response with respect to antigen cross-presentation and T cell cross-priming. Successful vaccination strategies rely on an optimally timed activation of the humoral and cellular immune system by using appropriate adjuvant stimulation. The LUD99-008 trial used the cancer testis antigen NY-ESO-1 formulated with ISCOMATRIX adjuvant injected into patients intramuscularly. It was shown that this vaccination strategy is a safe and highly potent activator of the humoral and cellular immune system. Using the RAYS technology, we analyzed in detail the humoral immune response in these patients before and after vaccination: during the course of repeated vaccinations with the adjuvant, antibody titers against NY-ESO-1 and cross-reactivity to LAGE 1A and B increased as an indicator of an enhanced immune response, whereas no antibody response could be detected after vaccination without the adjuvant. Analysis of single fragments of the NY-ESO-1 protein revealed that the humoral response was almost exclusively directed against the N-terminal fragments and the number of fragments and their length being recognized by the NY-ESO-1-specific antibodies increased during the course of vaccination. The humoral immune response mainly consisted of antibodies of the IgG1 and IgG3 subclass. We rarely found IgG2 and IgG4 subclass antibodies. Our results support the implication that targetspecific antibodies raised after vaccination contribute to the stimulation of an effective T cell response against the target antigen. IntroductionBesides surgery, chemotherapy and radiation therapy, immunotherapy has emerged in the past decade as supplementary approach to fight cancer (1). Due to its specificity and efficacy, immunotherapy ideally targets the tumor selectively and spares normal tissue. A prerequisite in the field of cancer immunotherapy is the identification and characterization of appropriate target antigens for therapeutic approaches. In modern tumor serology, the powerful SEREX-technology (serological identification of antigens by recombinant expression cloning) allowed for the identification of a multitude of new cancer antigens in various tumor entities by screening of tumor-derived gene expression libraries with high-titered IgG antibodies obtained from the sera of cancer patients. The international SEREX database (www2.licr.org/Cancer ImmunomeDB/) by now holds >2000 different gene entries of potentially cancer related antigens. One group of antigens, the so-called cancer/testis antigens (CTAs) has gained special interest among the characterized tumor-specific antigens, as they are only expressed in the immunologically privileged germline cells and various types of human cancers but not in normal tissue (2-4). Of particular interest in this regard is the CTA NY-ESO-1. It is the most immunogenic CTA discovered so far and frequently elicits spontaneous humoral and cellular immune responses in patients with NY-ESO-1 expressing tumors...

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“…In fact, several clinical trials targeting NY-ESO-1 and MAGE are ongoing and immune responses to these antigens have been induced in vaccinated patients (2,6,12,17).…”

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XAGE‐1 mRNA Expression in Prostate Cancer and Antibody Response in Patients

Koizumi

Noguchi

Sakaguchi

et al. 2005

Microbiology and Immunology

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To evaluate the feasibility of cancer vaccine targeting XAGE‐1, we investigated the expression of 4 XAGE‐1 transcript variants and the humoral immune response to XAGE‐1 in prostate cancer patients. XAGE‐1a, b, c, d mRNA expression was analyzed in 54 prostate cancer specimens and 8 specimens of benign prostate hypertrophy (BPH) by reverse transcription‐polymerase chain reaction (RT‐PCR). The humoral response to XAGE‐1 was investigated in sera obtained from 278 patients with prostate cancer and 40 healthy volunteers by enzyme‐linked immunosorbent assay (ELISA) using recombinant protein. XAGE‐1b mRNA expression was observed in 14 of 54 (26%) prostate cancer specimens, while XAGE‐1a, c, and d mRNA expressions were observed in 1, 1, and 3, respectively. None of the 4 XAGE‐1 transcript variants was observed in the 8 BPH specimens. Antibody against XAGE‐1 was detected in sera from 2 of 129 stage D2 patients, whereas none of sera from 149 patients with localized prostate cancer or lymph node metastasis had detectable XAGE‐1 antibody. No reactivity to XAGE‐1 was found in sera from the 40 healthy individuals.

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Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4+ and CD8+ T cell responses in humans

Cited by 396 publications

References 30 publications

Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

Dominant B cell epitope from NY‐ESO‐1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker

Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad antibody responses in humans, a RAYS-based analysis

XAGE‐1 mRNA Expression in Prostate Cancer and Antibody Response in Patients

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