Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine.

Hsueh, Eddy C.; Gupta, Rishab K.; Qi, Karen; Morton, Donald L.

doi:10.1200/jco.1998.16.9.2913

Cited by 145 publications

(64 citation statements)

References 27 publications

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“…Another report showed a decreased response to the target cells after absorption of serum samples in a plate coated with FBS (32). Some studies fail to account for the possible interference of antibodies to components of FBS when assaying antibodies to tumor derivatives (11,24,32). Our results suggest that if a cell line used to prepare a vaccine is cultured in FBS, one needs to exclude the presence of an antibody response to components of FBS before concluding that induction of tumorspecific antibodies has occurred.…”

Section: Discussionmentioning

confidence: 99%

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Identification of Tumor-Specific Antibodies in Patients With Breast Cancer Vaccinated With Gene-Modified Allogeneic Tumor Cells

Dols¹,

Meijer²,

Hu³

et al. 2003

Journal of Immunotherapy

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Summary: Thirty HLA-A2+ women with metastatic breast cancer received up to 14 vaccinations with MDA-MB-231-CD80, an HLA-A2 + allogeneic breast cancer cell line, which had been lipofected with the cDNA for the CD80 costimulatory molecule. Tumor cells were administered with BCG or GM-CSF as an adjuvant. Sera obtained before and after vaccination were analyzed for antibodies to tumor cell lysate, MUC1, HER2/neu and p53. Since the cell line was grown in fetal bovine serum (FBS), sera were also analyzed for antibodies to FBS. Eighteen of 24 patients for whom sera were available exhibited anti-FBS activity at baseline. Eleven of these 18 patients and all six patients without baseline anti-FBS activity showed an increased titer after vaccination. The anti-FBS activity required that serum samples be absorbed in excess FBS to detect specific antibodies to tumor cell lysate. A two-fold increase in the titer of IgG specific to tumor cell lysate was observed in 6 patients. Eight of 24 patients made an antibody response to HER-2/neu, four of 24 to MUC1 and one of 24 to p53. Although antibody production to a variety of tumor cell-associated antigens was detected our results suggest that a whole cell vaccine comprising a CD80-transfected allogeneic breast cancer cell line with adjuvant BCG or GM-CSF was not a reliable method to induce significant antibody responses in women with advanced breast cancer. Key Words: Antibodies-BS-ER-2/neu-MB-231-UC1.The potential value of a vaccine that induces the production of high titer antibodies to tumor-associated antigens is illustrated by the successful treatment of patients with breast cancer and non-Hodgkins lymphoma (NHL) with exogenously administered monoclonal antibodies. Women with metastatic breast cancer that overexpresses Her2/neu experience increased survival after treatment with trastuzumab (Herceptin; Genentech Inc., South San Francisco, CA, U.S.A.), a humanized monoclonal antibody with high affinity for HER-2/neu (1,2), when given with chemotherapy (3). The FDA has also approved anti-CD20, rituximab, for the treatment of patients with CD20 + NHL (4). Furthermore, women with breast cancer who develop a natural immune response to MUC1 (5) and CEA (6) survive longer than women who fail to develop an antibody response. Production of tuSupported in part by NCI RO3 CA70299-02 (awarded to W. J. Urba) and grants from the Chiles Foundation, the Collins Medical Trust, the M.J. Murdock Charitable Trust, and a generous gift from the Flora Family Foundation.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, women with breast cancer who develop a natural immune response to MUC1 (5) and CEA (6) survive longer than women who fail to develop an antibody response. Production of tu-mor-specific antibodies after vaccination also correlates with improved survival in patients with melanoma (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Identification of Tumor-Specific Antibodies in Patients With Breast Cancer Vaccinated With Gene-Modified Allogeneic Tumor Cells

Dols¹,

Meijer²,

Hu³

et al. 2003

Journal of Immunotherapy

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“…In spite of this, a much larger percentage of patients treated with melanoma vaccines develop definite immune reactions. Although in most cases these reactions fail to translate into clinical tumour regressions, improved survival has been repeatedly reported for those patients who develop anti-melanoma immune responses (Bystryn et al, 1992;Livingston et al, 1994;Hsueh et al, 1998;Baars et al, 2000). These observations have led to several ongoing studies for the evaluation of the adjuvant role of active immunotherapy for high-risk melanoma patients.…”

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confidence: 99%

Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV)

Lotem¹,

Peretz²,

Drize³

et al. 2002

Br J Cancer

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This study evaluates the overall survival and disease free survival of melanoma patients that were treated with an autologous melanoma cell vaccine, administered as a post-operative adjuvant. Included are 43 patients with totally resected metastatic melanoma (28-AJCC stage III, 15-AJCC stage IV), with a median follow up of 34 months (6 -62). The treatment consisted of eight doses of a vaccine made of 10 -25610 6 autologous melanoma cells either released from the surgical specimen or grown in cell cultures. Tumour cells were conjugated with hapten dinitrophenyl, mixed with Bacille Calmette Guérin and irradiated to 110 Gy. Both disease free survival and overall survival were found to be correlated with intensity of evolving delayed type hypersensitivity to subcutaneous injection of unmodified melanoma cells. Patients with a delayed type hypersensitivity reaction of 510 mm had a median disease free survival of 17 months (mean 35 months) and a mean overall survival of 63 months (median not reached). In contrast, patients with a negative or weak delayed type hypersensitivity had a median disease free survival of 9 months (relative risk of recurrence=4.5, P=0.001), and a median overall survival of 16 months (relative risk of death=15, P=0.001). Stage III patients with a positive delayed type hypersensitivity reaction had an improved disease free survival of 16 months and a mean overall survival of 38 months, whereas patients with a negative delayed type hypersensitivity had a median disease free survival of 7 months (relative risk=4.5, P=0.02) and a median overall survival of 16 months (relative risk=9.5, P=0.005). The adjuvant administration of autologous melanoma vaccine was associated with improved disease-free and overall survival to selected patients who successfully attained anti-melanoma reactivity as detected by positive delayed type hypersensitivity reactions to unmodified melanoma cells.

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“…La découverte d'antigènes communs exprimés par les mélanomes et la difficulté que représente la purification de cellules tumorales ont conduit à utiliser en thérapeutique des lignées allogéniques de méla-nome portant des antigènes fréquemment exprimés. Deux vaccins cellulaires établis à partir de lignées allogéniques semblent montrer une efficacité en situation adjuvante, et à un moindre niveau en situation métastatique, dans des études de phases II [11][12][13] ; ils sont actuellement en cours de validation dans le cadre d'une étude de phase III. La découverte que la transfection de cellules tumorales par un gène codant pour une cytokine (IL-2, IFNα, GMCSF [granulocyte-macrophage colony-stimulating factor]), IL-12…) pouvait rendre ces cellules plus immunogéniques dans des modèles animaux a déclenché le lancement d'essais thérapeutiques : leurs résultats sont toutefois décevants pour l'instant [14], sauf en ce qui concerne l'utilisation de cellules transfectées avec le gène codant pour le GMCSF, qui s'accompagne de fortes réponses immunologiques locales et dans les tumeurs, et de quelques réponses cliniques [15].…”

Section: Vaccination Par Cellules Tumoralesunclassified

Stratégies vaccinales contre le mélanome

Ghiringhelli

Zitvogel

2006

Med Sci (Paris)

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L'incidence du mélanome est en augmentation constante, le traitement de choix restant la résection chirurgicale quand la maladie est localisée. Cependant, lorsque la lésion est profonde ou que des ganglions satellites sont envahis, les patients restent exposés au risque d'évolution métastatique ; ils peuvent alors bénéficier d'un traitement par l'interféron α (IFNα), qui diminue le risque de récidive [1]. La maladie métastatique nécessite quant à elle un traitement systémique : la chimiothérapie donne des taux de réponses d'environ 20 %, et n'augmente pas la médiane de survie, qui reste aux alentours de 9 mois [2]. Le système immunitaire joue un rôle dans l'évolution naturelle du mélanome : en effet, l'incidence du méla-nome augmente en cas d'immunosuppression, certains mélanomes régressent spontanément et l'infiltration de la tumeur par les lymphocytes T semble être un facteur de bon pronostic [3]. Toutes ces données ont amené à penser que des stratégies immunologiques vaccinales pourraient améliorer le pronostic des mélanomes localement évolués et métastatiques. À l'heure actuelle, l'immunothérapie du mélanome se résume en pratique clinique à l'utilisation de l'IFNα en situation adjuvante [1]. En situation métastati-que, l'IL-2 (interleukine-2) et l'IFNα entraînent dans 15 % à 20 % des cas une réponse clinique souvent partielle et de courte durée, même s'il existe de rares rémissions complètes prolongées. Thérapies vaccinales passives par injection de lymphocytes T spécifiquesLa découverte de lymphocytes T infiltrant (TIL) les tumeurs et capables de détruire in vitro des cellules de mélanome a suggéré qu'un transfert passif de lymphocytes T activés ex vivo pourrait avoir un effet thé-rapeutique. Les premiers essais cliniques consistaient à injecter, en association avec des injections d'IL2, des lymphocytes T provenant de la tumeur primaire et amplifiés par de fortes doses d'IL2. Ces procédés ont entraîné environ 20 % de réponses objectives [4], mais l'expansion de lymphocytes T antitumoraux n'est possible que dans 40 % des cas. De nouvelles techniques permettent de mieux sélec-tionner les lymphocytes T antitumoraux : ainsi, les TIL peuvent être cultivés avec des cellules tumorales autologues ou allogéniques pour augmenter leur spécificité antitumorale ; ils peuvent également être stimulés par des peptides issus d'antigènes tumoraux, pour induire une réponse clonale contre un antigène particulier ;

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Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine.

Abstract: PMCV induces both humoral and cell-mediated immune responses to melanoma-associated tumor antigens, the type and strength of which appear to be directly related to its therapeutic efficacy.

Cited by 145 publications

References 27 publications

Identification of Tumor-Specific Antibodies in Patients With Breast Cancer Vaccinated With Gene-Modified Allogeneic Tumor Cells

Identification of Tumor-Specific Antibodies in Patients With Breast Cancer Vaccinated With Gene-Modified Allogeneic Tumor Cells

Autologous cell vaccine as a post operative adjuvant treatment for high-risk melanoma patients (AJCC stages III and IV)

Stratégies vaccinales contre le mélanome

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