Immunotherapy of melanoma

Parmiani, Giorgio; Castelli, Chiara; Rivoltini, Licia; Casati, Chiara; Tully, Glenn; Novellino, Luisa; Patuzzo, Andrea; Tosi, Diego; Anichini, Andrea; Santinami, Mario

doi:10.1016/j.semcancer.2003.09.001

Cited by 48 publications

(34 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2 The observation of spontaneous immune responses in melanoma patients have inspired various efforts of immune therapy. 3,4 To date, most melanoma vaccines have made use of defined melanoma antigens like MAGE-1 and -3, MART-1/Melan A and gp100. [5][6][7][8][9] Although promising responses have been obtained, the defined melanoma antigens are not essential for tumor survival, and genetic alterations may lead to tumor escape.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

et al. 2006

View full text Add to dashboard Cite

We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-g ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination. Cancer Gene Therapy (2006) 13, 905-918.

show abstract

Section: Introductionmentioning

confidence: 99%

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

et al. 2006

View full text Add to dashboard Cite

show abstract

“…I t is generally thought that tumor cells can be killed by antitumor effector lymphocytes (1)(2)(3)(4)(5)(6)(7)(8). Different lymphocyte subsets are considered to be involved in this process, including CTL, ␥␦ T cells, and NK cells (1)(2)(3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

“…Different lymphocyte subsets are considered to be involved in this process, including CTL, ␥␦ T cells, and NK cells (1)(2)(3)(4)(5)(6)(7)(8). However, it is evident that tumor cells can elude immune surveillance by several means (2)(3)(4)(5).…”

mentioning

confidence: 99%

“…However, it is evident that tumor cells can elude immune surveillance by several means (2)(3)(4)(5). Indeed, CTL-mediated control can be broken out as tumor cells down-regulate HLA class I expression affecting the recognition of tumor Ag peptides (2)(3)(4)(5). This can be also accomplished by the lack, at the tumor cell surface, of costimulatory molecules and/or by the production of immunosuppressive cytokines such as TGF-␤, or by the induction of suppressor T cells (9,10).…”

mentioning

confidence: 99%

“…It has been also proposed that activation-induced cell death can be triggered in ␥␦ T lymphocytes during their interaction with lymphoma target cells, and that the inhibition of apoptosis, by the use of specific blockers of caspase 3, can increase the antitumor effect exerted by ␥␦ T cells (12). More recently, it has been shown that melanomas can release vesicles containing Fas ligand (FasL) 3 that lead to lymphocyte cell death upon interaction with Fas Ag (13).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Tumor-Induced Apoptosis of Human IL-2-Activated NK Cells: Role of Natural Cytotoxicity Receptors

Poggi¹,

Massaro

Negrini

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

We provide evidence that tumor cells can induce apoptosis of NK cells by engaging the natural cytotoxicity receptors (NCR) NKp30, NKp44, and NKp46. Indeed, the binding between NCR on NK cells and their putative ligands on tumor target cells led to NK cell apoptosis, and this event was abolished by blocking NCR/NCR-ligand interaction by anti-NCR-specific mAbs. The engagement of NCR induced up-regulation of Fas ligand (FasL) mRNA, FasL protein synthesis, and release. In turn, FasL interacting with Fas at NK cell surface causes NK cell suicide, as apoptosis of NK cells was inhibited by blocking FasL/Fas interaction with specific mAbs. Interestingly, NK cell apoptosis, but not killing of tumor target cells, is inhibited by cyclosporin A, suggesting that apoptosis and cytolysis are regulated by different biochemical pathways. These findings indicate that NCR are not only triggering molecules essential for antitumor activity, but also surface receptors involved in NK cell suicide.

show abstract

Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target

Spanjaard

Whren

Graves

et al. 2006

Intl Journal of Cancer

View full text Add to dashboard Cite

Incidence of melanoma continues to rise, and a better understanding of its genetics will be critical to improve diagnosis and develop new treatments. Here, we search for novel melanoma-specific genes that may serve as biomarkers and therapeutic targets by using an in vitro genetic screen. One identified cDNA encoded TROY, a member of the tumor necrosis factor receptor superfamily (TNFRSF). TROY is widely expressed during embryogenesis, but in adults expression is restricted to hair follicles and brain. However, TROY had never been associated with melanoma, and it was selected for further study. First we show that expression in melanoma is specific by semiquantitative RT-PCR analysis of a large panel of established tumor cell lines. Next, specificity of expression was evaluated by immunohistochemistry analysis of primary cell cultures and patient tissues. TROY is expressed in 2/2 primary melanoma cells and 45/45 melanoma tissue samples (p < 0.0001). With the exception of sebaceous glands, TROY is not expressed in normal skin biopsies (p < 0.0001) or primary skin cell cultures that contain keratinocytes and epidermal melanocytes, nor is it expressed in other skin tumor cells (p < 0.0001). Finally, we show that TROY regulates melanoma growth, because replication of melanoma cells with reduced TROY levels through treatment with short-interfering RNA was significantly decreased relative to control cells (p < 0.004). In summary, TROY is the first TNFRSF member that is a biomarker for melanoma. TROY also presents a potentially novel cell surface signaling target for inhibitors, cell and/or antibody-based immunotherapies. ' 2006 Wiley-Liss, Inc.

show abstract

Immunotherapy of melanoma

Cited by 48 publications

References 58 publications

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

Tumor-Induced Apoptosis of Human IL-2-Activated NK Cells: Role of Natural Cytotoxicity Receptors

Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target

Contact Info

Product

Resources

About