Search PubMed⌕ Search

Biomedical subjects

Jean-Claude Bystryn

Publications and source records attributed to Jean-Claude Bystryn.

At least 19 recordsLinked to original sources
PubMed2006

Cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in patients with melanoma: a potential marker of response to immunotherapy?

Simple, noninvasive methods are needed to follow effectiveness of new treatments in patients with melanoma. In our study, we examined cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in melanoma patients during immunotherapy. Sera of 117 patients were assayed for CYT-MAA by double-sandwich ELISA before and during treatment with a polyvalent, shed antigen, melanoma vaccine. Vaccine-treated patients included 30 with American Joint Committee on Cancer (AJCC) stage IIb or IIIa, 30 with stage IIc, IIIb or IIIc, 30 with resected stage IV and 27 with measurable stage IV disease. Prior to vaccine therapy, 63% of patients had elevated serum CYT-MAA with high levels of antigen in all disease stages. After initiation of therapy, the level declined in more than 90% of the positive patients and fell below the positive cut-off in 56% of these patients within 5 months. By contrast, there was no decline in CYT-MAA serum level in 11 patients who served as untreated controls with melanoma. Multivariate analysis of the treated patients using accelerated failure time Weibull models adjusted for stage and age showed that patients whose CYT-MAA serum level remained elevated during treatment were approximately 3 times more likely to recur or progress than patients who were consistently below the positive cut-off (hazard ratio = 3.42, 95% CI [1.38, 8.47], p = 0.0079). Measurement of CYT-MAA serum level appears to show potential as an early marker of prognosis in patients with stages IIb to IV melanoma. Measurement of CYT-MAA serum level during therapy could provide an intermediate marker of response in these patients.

Adolescent↗
PubMed2005

Topical imiquimod is a potent adjuvant to a weakly-immunogenic protein prototype vaccine.

A major challenge in the development of more effective vaccines for cancer and other diseases is the development of potent adjuvants that can strongly, simply and safely enhance vaccine immunogenicity. Adjuvants that preferentially enhance Th1 type of responses are particularly desirable, as these responses are believed to play the major role in immune resistance to cancer. This study describes the ability of topical application of imiquimod to act as a potent, safe and simple vaccine adjuvant in mice. Groups of C57BL/6 mice were immunized subcutaneously with ovalbumin (OVA, 0.1mg/dose) weekly x 4. Imiquimod in a 5% cream formulation was rubbed into the skin over the injection site for 15s to give a dose of approximately 1mg/treatment following each immunization. Control mice were immunized with OVA alone, with irradiated E.G7-OVA cells (that express ovalbumin), with OVA encapsulated in liposomes, or to PBS. Topical imiquimod enhanced anti-OVA antibody responses 100-fold and markedly increased cellular responses compared to mice not given imiquimod. The responses were shifted towards a Th1 phenotype, with marked enhancement of IgG2a, IgG2b, and CD8+ T cell responses and concomitant suppression of IgM and IgG1 responses. More frequent topical applications of imiquimod further enhanced both antibody and cellular responses. There was no detectable local or systemic toxicity associated with treatment. These results indicate that topical imiquimod can safely and strongly enhance both antibody and CD8+ T cell response to OVA immunization, and suggest that it may provide a simple, safe and effective way to enhance the immunogenicity of vaccines in general.

Adjuvants, Immunologic↗
PubMed2005

Interleukin-2/liposomes potentiate immune responses to a soluble protein cancer vaccine in mice.

A critical element in improving the potency of cancer vaccines, especially pure protein or peptide antigens, is to develop procedures that can strongly but safely increase their ability to induce immune responses. Here, we describe that encapsulation of a pure protein antigen and interleukin-2 (IL-2) together into liposomes significantly improves immune responses and tumor protection. Groups of C57Bl/6 mice were immunized weekly x4 with -0.1 mg of ovalbumin (OVA) injected subcutaneously in PBS or encapsulated in liposomes with or without human recombinant IL-2. Control groups included mice immunized to irradiated E.G7-OVA cells (that express ovalbumin), or to PBS. Sera were collected and pooled by immunization group at baseline and at weeks 2 and 4 to measure antibody responses to OVA by ELISA. Splenocytes obtained at week 4 were tested for anti-OVA cellular responses by ELISPOT. Mice were then challenged to a lethal dose of E.G7-OVA cells to measure tumor-protective immunity. IL-2 liposomes caused no detectable toxicity. Antibody, CD8(+) T cell, and tumor-protective immune responses were markedly enhanced in mice immunized to OVA + IL-2 in liposomes compared to mice immunized to OVA, either alone or encapsulated into liposomes without IL-2. These results indicate that IL-2 liposomes enhance antibody, cellular, and tumor-protective immune responses to immunization with a soluble protein. This may provide a simple, safe, and effective way to enhance the immunogenicity of vaccines that consist of pure protein antigens.

Animals↗
PubMed2005

Emerging melanoma vaccines.

No satisfactory treatment currently exists for melanoma once it has spread beyond its original site. At present, the only FDA-approved treatment for advanced melanoma is IFN-alpha2b. Vaccines are an experimental therapy intended to stimulate the immune system to react more strongly against patients' own melanoma cells, thereby destroying the tumour or slowing its progression. Unfortunately, the exact tumour antigens that can stimulate an effective tumour-protective response in humans remain unknown. The approach that is increasingly followed to circumvent this problem is to prepare polyvalent vaccines containing a variety of melanoma antigens, as the greater the number of antigens in a vaccine, the greater the chance it will contain the correct antigen(s) to stimulate an antitumour response. Two recent randomised trials suggest that this approach results in vaccines that can be clinically effective. One is a double-blind, placebo-controlled trial of a polyvalent, shed antigen melanoma vaccine developed by Bystryn and licenced to NeoVac; the other is a larger randomised trial of Melacine (Corixa Corp.), a vaccine prepared from the lysate of two melanoma cell lines adjuvanted with Detox, which was developed by Mitchell and commercialized by Corixa. In both cases, tumour progression was delayed in the vaccine-treated patients, although in the latter trial, this was only observed in patients with certain human leukocyte antigen phenotypes. Several other vaccines are currently in Phase III trials, but the results of these trials are still pending. The major issues that need to be addressed are designing more effective melanoma vaccines with a mix of melanoma-associated antigens that can stimulate clinically beneficial antitumour immune responses, and finding an adjuvant that can safely, easily and powerfully boost the frequency and magnitude of these responses.

Animals↗
PubMed2005

Melanoma vaccines: what we know so far.

Vaccines are a promising but still experimental treatment for melanoma. They are intended to stimulate immune responses against melanoma and by so doing, increase resistance against and slow the progression of this cancer. Key requirements for vaccines to be effective are that they contain antigens that can stimulate tumor-protective immune responses and that some of these antigens are present on the tumor to be treated. Unfortunately, these antigens are still not known. To circumvent this problem, polyvalent vaccines can be constructed containing a broad array of melanoma-associated antigens. Several strategies are available to construct such polyvalent vaccines; each has advantages and disadvantages. Clinical trials have shown that vaccines are safe to use and have much less toxicity than current therapy for melanoma. Vaccines can stimulate both antibody and T-cell responses against melanoma, with the type of response induced, its frequency, and its magnitude depending on the vaccine and the adjuvant agent used. A growing body of evidence suggests that vaccines can be clinically effective. This evidence includes correlations between vaccine-induced antibody or T-cell responses and improved clinical outcome, clearance of melanoma markers from the circulation, improved survival compared to historical controls, and most convincingly, two randomized trials in which the recurrence-free survival of vaccine-treated patients was significantly longer than that of control groups.

Antibody Formation↗
PubMed2004

Heterogeneous antibody response to polyvalent melanoma vaccines in syngeneic mice.

In this study, a human melanoma vaccine induced antibody responses in mice that varied significantly from animal to animal. BALB/c mice were immunized to a xenogenic human polyvalent melanoma vaccine that has been used in phase II clinical trials in over 600 patients. Mice were bled biweekly for up to 6 weeks to measure antibody responses. IgG antibody responses to the melanoma vaccine components were detectable within 2 weeks but were much stronger at 4 and 6 weeks. When the pooled sera were further analyzed by Western blot, a complex pattern of antigens was detected. When individual sera from identically immunized mice were assayed by Western blot, a consistent, reproducible pattern of antigen recognition was not seen. Rather, we found significantly different antibody responses among the mice. Both the intensity of antibody responses and the pattern of antigens recognized varied from animal to animal. Although there appeared to be immunodominant antigens that produced antibody responses in most mice, no single antigen induced antibody responses in all mice. These results demonstrate that polyvalent vaccines induce heterogeneous antibody responses in mice treated identically. Analysis of the response of selected melanoma patients immunized to the same vaccine revealed similar antibody responses to the antigens in the melanoma vaccine. Heterogeneity may hamper interpretation of vaccine immunogenicity and relevant tumor antigens in humans.

Animals↗
PubMed2003

Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis.

OBJECTIVE: To define comprehensive criteria for the classification and differential diagnosis of tumid lupus erythematosus (LE). METHODS: A prospective study of patients fulfilling the classical description of tumid LE was performed. Clinical evaluation, histopathologic and direct immunofluorescence analyses of skin specimens, and serologic evaluation were conducted. The inflammatory cell infiltrate was quantitatively investigated by immunohistochemical analysis of fresh frozen skin specimens using multiple lymphocytic markers. RESULTS: Fifteen patients were followed for a mean of 7 years. Smooth, indurated, nonscarring, pink to violaceous papules, plaques, or nodules, devoid of surface changes were distributed on sun exposed sites. The mean lesion duration was 2 years, female:male ratio was 8:7, and racial distribution was 11 white, 2 Hispanic, and 2 African American patients. Histopathologic findings included a superficial and deep, perivascular, and frequently periadnexal infiltrate of lymphocytes, mucin deposition throughout the dermis, and absent to focal dermal-epidermal junctional involvement. Direct immunofluorescence immunoreactants and low titer antinuclear antibodies were variably present. Immunohistochemical findings included a predominance of pan-T cell marker CD3-expressing (78.0% +/- 6.3%) T lymphocytes. Most were CD4 expressing (82.7% +/- 8.0%) helper T cells; a minority were CD8 expressing (31.3% +/- 14.0%) cytotoxic T cells. The CD4:CD8 ratio was 3.1 (+/-1.3):1. One patient developed systemic LE and one a discoid LE lesion. CONCLUSION: Comprehensive clinical, histopathologic, and immunohistochemical criteria for the classification of tumid LE are proposed that differentiate tumid LE from other cutaneous disorders that may be clinically and histologically indistinguishable. The chronic, benign course indicates that tumid LE be classified as a form of chronic cutaneous LE, although it may be a cutaneous feature of systemic LE.

Adult↗
PubMed2003

Improved identification of potentially dangerous pigmented skin lesions by computerized image analysis.

BACKGROUND: Melanoma is completely curable if resected early. Unfortunately, early melanoma can be difficult to differentiate from other pigmented lesions. Computerized image analysis instruments have now been developed to assist in determining whether a pigmented lesion is potentially dangerous and requires biopsy. To evaluate whether one such instrument can improve the management of pigmented lesions, we obtained biopsy specimens from 52 pigmented lesions that appeared clinically benign to an experienced dermatologist but were suspicious by image analysis. OBSERVATION: Histologically, 9 (17%) of the lesions that were removed based solely on computer recommendation were potentially dangerous and should have been removed. These included 1 malignant melanoma in situ and 8 dysplastic nevi with moderate to severe cytologic atypia. CONCLUSION: The results of the present study indicate that computerized image analysis can improve the evaluation of pigmented skin lesions by identifying clinically unsuspicious, but potentially dangerous, lesions that might have otherwise have been neglected.

Biopsy, Needle↗
PubMed2003

Vaccine-induced CD8+ T-cell responses to MAGE-3 correlate with clinical outcome in patients with melanoma.

PURPOSE: Vaccine-induced antitumor CD8+ T-cell responses are believed to play an important role in increasing resistance to melanoma. The following study was conducted to examine whether these responses are associated with improved clinical outcome in melanoma vaccine-treated patients. EXPERIMENTAL DESIGN: We measured CD8+ T-cell responses to gp100, MART-1, MAGE-3, and tyrosinase by enzyme-linked immunospot assay in peripheral blood of 131 HLA-A*01- or HLA-A*02-positive melanoma patients before and after immunization to a polyvalent, shed antigen, melanoma vaccine, and correlated the results with clinical outcome. RESULTS: Fifty-six percent of patients had a vaccine-induced CD8+ T-cell response to at least one of the four antigens. Recurrences were significantly reduced in patients with vaccine-induced responses to MAGE-3 (hazard ratio, 0.42; 95% confidence interval, 0.18-0.99; P = 0.03) by the Cox proportional hazard model but were unrelated to responses to the other three antigens. Patients with a preexisting response to any of the four antigens were significantly more likely to have a further vaccine-boosted response to that same antigen (P < 0.0001-0.036). CONCLUSIONS: There was a correlation between vaccine-induced CD8+ T-cell responses to melanoma-associated antigens and improved clinical outcome, but the correlation depended on the antigen against which the response is directed. The only significant correlation was with responses to MAGE-3.

Adult↗
PubMed2003

Changes in the presence of multiple markers of circulating melanoma cells correlate with clinical outcome in patients with melanoma.

PURPOSE: Melanoma cells can be found in the circulation of patients with melanoma. The following study was conducted to examine whether changes in their presence could provide an early marker of response to therapy. EXPERIMENTAL DESIGN: We measured the presence of several markers of melanoma cells in the peripheral blood of 118 patients with resected stage IIb, III, or IV melanoma before and after immunotherapy with a polyvalent, shed antigen, melanoma vaccine using reverse transcription-PCR assays for tyrosinase, gp100, MART-1, and MAGE-3. Assays were conducted at baseline and after 3, 5, and 11 months of therapy. RESULTS: Overall, 47% of patients were positive for at least one marker during the study. Before vaccine treatment, circulating melanoma cell markers were present in 23% of patients. After 5 and 7 months of vaccine therapy, the proportion of patients with circulating markers decreased by 27% and 55%, respectively (P for trend = 0.02). The recurrence-free survival of patients whose melanoma cell markers disappeared during vaccine treatment was significantly longer than that of patients in whom they increased, i.e., the percentage of patients who were recurrence free at 1 year was 80% versus 58% (P = 0.03). CONCLUSIONS: Therapy with a polyvalent melanoma vaccine was associated with clearance of melanoma cell markers from the circulation, and the clearance was associated with an improved prognosis. These findings suggest that the sequential assay of tumor cells in the circulation by reverse transcription-PCR may provide an early indication of the effectiveness of cancer therapy.

Adolescent↗