Survey of naturally occurring CD4
            <sup>+</sup>
            T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses

Gnjatic, Sacha; Atanackovic, Djordje; Jäger, Elke; Matsuo, Masatsugu; Selvakumar, A.; Altorki, Nasser K.; Maki, Robert G.; Dupont, Bo; Ritter, Gerd; Chen, Yao‐Tseng; Knuth, Alexander; Old, Lloyd J.

doi:10.1073/pnas.1133324100

Cited by 181 publications

(192 citation statements)

References 23 publications

(27 reference statements)

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“…It was also shown that patients with high antibody titers against NY-ESO-1 produce an effective CD8 + T cell response (22). Moreover, a clear correlation of an NY-ESO-1-specific antibody response and NY-ESO-1-specific CD4 + T cells was described (34). In summary, an orchestrated interaction of different parts of the immune system seems to be necessary to generate an efficient and durable immune response.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…In NY-ESO-1-expressing gastric tumors, the overall frequency of antibody positivity was 11%, but it increased with disease progression (34). Importantly, humoral immune response to NY-ESO-1 has been shown to predict both CD8 and CD4 T-cell responses to NY-ESO-1 (35,36).…”

Section: Discussionmentioning

confidence: 99%

NY-ESO-1 Expression in Meningioma Suggests a Rationale for New Immunotherapeutic Approaches

Baía

Caballero

et al. 2013

Cancer Immunology Research

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Meningiomas are the most common primary intracranial tumors. Surgical resection remains the treatment of choice for these tumors. However, a significant number of tumors are not surgically accessible, recur, or become malignant, necessitating the repetition of surgery and sometimes radiation. Chemotherapy is rarely used and is generally not recognized as an effective treatment. Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in patients with cancer and this feature makes them attractive targets for immunotherapy-based approaches. We analyzed mRNA expression of 37 testis-restricted CT genes in a discovery set of 18 meningiomas by reverse transcription PCR. The overall frequency of expression of CT genes ranged from 5.6% to 27.8%. The most frequently expressed was NY-ESO-1, in 5 patients (27.8%). We subsequently analyzed NY-ESO-1 protein expression in a larger set of meningiomas by immunohistochemistry and found expression in 108 of 110 cases. In some cases, NY-ESO-1 expression was diffused and homogenous, but in most instances it was heterogeneous. Importantly, NY-ESO-1 expression was positively correlated with higher grade and patients presenting with higher levels of NY-ESO-1 staining had significantly worse disease-free and overall survival. We have also shown that NY-ESO-1 expression may lead to humoral immune response in patients with meningioma. Considering the limited treatment options for patients with meningioma, the potential of NY-ESO-1-based immunotherapy should be explored. Cancer Immunol Res; 1(5); 296-302. Ó2013 AACR.

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“…The highly restricted expression pattern of NY-ESO-1 in normal tissues (testis), its frequent expression in a wide variety of cancers, and the spontaneous humoral and cellular immune responses elicited by NY-ESO-1 in a subset of patients with NY-ESO-1-expressing tumors are highly favorable characteristics for a vaccine target (1,5,6,16). Immunological assays to detect antibody and CD4 and CD8 T cell responses to NY-ESO-1 are well advanced and provide a secure basis for monitoring spontaneous and vaccine-induced immune responses and for comparing the immunogenicity of different NY-ESO-1 vaccine constructs (4,16,17) .…”

Section: Discussionmentioning

confidence: 99%

“…Spontaneous immune responses involving antibody as well as CD4 and CD8 T cells directed against a broad range of MHC class I-and class II-restricted NY-ESO-1 peptides have been observed in patients with advanced NY-ESO-1-expressing tumors (4)(5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients

Jäger

Karbach

Gnjatic

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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NY-ESO-1 is a cancer͞testis antigen expressed in a range of human malignancies, and a number of vaccine strategies targeting NY-ESO-1 are being developed. In the present study, the safety and immunogenicity of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 were analyzed in a series of 36 patients with a range of different tumor types. Each construct was first tested individually at two different dose levels and then in a prime-boost setting with recombinant vaccinia-NY-ESO-1 followed by recombinant fowlpox-NY-ESO-1. The vaccines were well tolerated either individually or together. NY-ESO-1-specific antibody responses and͞or specific CD8 and CD4 T cell responses directed against a broad range of NY-ESO-1 epitopes were induced by a course of at least four vaccinations at monthly intervals in a high proportion of patients. CD8 T cell clones derived from five vaccinated patients were shown to lyse NY-ESO-1-expressing melanoma target cells. In several patients with melanoma, there was a strong impression that the natural course of the disease was favorably influenced by vaccination.antibody response ͉ NY-ESO-1 recombinant vaccine ͉ T cell response ͉ tumor reactivity

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Survey of naturally occurring CD4 ⁺ T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses

Abstract: NY-ESO-1 is one of the most immunogenic proteins described in

Cited by 181 publications

References 23 publications

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

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

NY-ESO-1 Expression in Meningioma Suggests a Rationale for New Immunotherapeutic Approaches

Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients

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Survey of naturally occurring CD4 + T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses

Abstract: NY-ESO-1 is one of the most immunogenic proteins described in

Cited by 181 publications

References 23 publications

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

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

NY-ESO-1 Expression in Meningioma Suggests a Rationale for New Immunotherapeutic Approaches

Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients

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Product

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Survey of naturally occurring CD4 ⁺ T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses