ES2372713T3 - Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente. - Google Patents

Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente. Download PDF

Info

Publication number
ES2372713T3
ES2372713T3 ES08701232T ES08701232T ES2372713T3 ES 2372713 T3 ES2372713 T3 ES 2372713T3 ES 08701232 T ES08701232 T ES 08701232T ES 08701232 T ES08701232 T ES 08701232T ES 2372713 T3 ES2372713 T3 ES 2372713T3
Authority
ES
Spain
Prior art keywords
cells
lymphocytes
antigens
tumor
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES08701232T
Other languages
English (en)
Spanish (es)
Inventor
Alexei Kirkin
Karine Dzhandzhugazyan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cytovac AS
Original Assignee
Cytovac AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cytovac AS filed Critical Cytovac AS
Application granted granted Critical
Publication of ES2372713T3 publication Critical patent/ES2372713T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0636T lymphocytes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/10Cellular immunotherapy characterised by the cell type used
    • A61K40/11T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/20Cellular immunotherapy characterised by the effect or the function of the cells
    • A61K40/24Antigen-presenting cells [APC]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/40Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41Vertebrate antigens
    • A61K40/42Cancer antigens
    • A61K40/4267Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06Animal cells or tissues; Human cells or tissues
    • C12N5/0602Vertebrate cells
    • C12N5/0634Cells from the blood or the immune system
    • C12N5/0636T lymphocytes
    • C12N5/0637Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/57Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/572Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 cytotoxic response
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/06Anti-neoplasic drugs, anti-retroviral drugs, e.g. azacytidine, cyclophosphamide
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2501/00Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20Cytokines; Chemokines
    • C12N2501/23Interleukins [IL]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00Coculture with; Conditioned medium produced by
    • C12N2502/11Coculture with; Conditioned medium produced by blood or immune system cells
    • C12N2502/1121Dendritic cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Oncology (AREA)
  • Mycology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
ES08701232T 2007-01-03 2008-01-03 Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente. Active ES2372713T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0700058.1A GB0700058D0 (en) 2007-01-03 2007-01-03 Anti-tumor vaccine based on normal cells
GB0700058 2007-01-03

Publications (1)

Publication Number Publication Date
ES2372713T3 true ES2372713T3 (es) 2012-01-25

Family

ID=37759205

Family Applications (1)

Application Number Title Priority Date Filing Date
ES08701232T Active ES2372713T3 (es) 2007-01-03 2008-01-03 Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente.

Country Status (14)

Country Link
US (2) US10023839B2 (enExample)
EP (1) EP2102331B1 (enExample)
JP (1) JP5452231B2 (enExample)
AT (1) ATE522600T1 (enExample)
AU (1) AU2008203730B2 (enExample)
CY (1) CY1112668T1 (enExample)
DK (1) DK2102331T3 (enExample)
ES (1) ES2372713T3 (enExample)
GB (1) GB0700058D0 (enExample)
HR (1) HRP20110899T1 (enExample)
PL (1) PL2102331T3 (enExample)
PT (1) PT2102331E (enExample)
SI (1) SI2102331T1 (enExample)
WO (1) WO2008081035A1 (enExample)

Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA011421B1 (ru) * 2008-08-26 2009-02-27 Петр Генриевич ЛОХОВ Способ получения противоопухолевой вакцины
US8666674B2 (en) 2009-07-28 2014-03-04 Promising Future, Llc Pairing processes for preparing reactive cytotoxic T cells
US8467973B2 (en) 2009-07-28 2013-06-18 Promising Future, Llc Pairing processes for preparing alloreactive cytotoxic T cells
EP2494038B1 (en) 2009-10-27 2019-06-26 Immunicum AB Method for proliferation of antigen-specific t cells
GB201013443D0 (en) 2010-08-11 2010-09-22 Cytovac As Compositions and methods for producing dendritic cells
US10426740B1 (en) 2010-08-18 2019-10-01 Avm Biotechnology, Llc Compositions and methods to inhibit stem cell and progenitor cell binding to lymphoid tissue and for regenerating germinal centers in lymphatic tissues
KR102349677B1 (ko) 2015-05-28 2022-01-12 카이트 파마 인코포레이티드 T 세포 요법을 위해 환자를 컨디셔닝하는 방법
CA2986793A1 (en) 2015-05-28 2016-12-01 Kite Pharma, Inc. Diagnostic methods for t cell therapy
KR20180063320A (ko) 2015-10-20 2018-06-11 카이트 파마 인코포레이티드 T 세포 요법을 위한 t 세포를 제조하는 방법
CA3019650C (en) 2016-04-01 2023-07-25 Kite Pharma, Inc. Chimeric receptors and methods of use thereof
TWI795133B (zh) 2016-04-01 2023-03-01 美商凱特製藥公司 Bcma結合分子類及彼等之用途
ES2891578T3 (es) 2016-04-01 2022-01-28 Kite Pharma Inc Antígeno quimérico y receptores de células T y métodos de uso
TWI785009B (zh) 2017-02-14 2022-12-01 美商凱特製藥公司 Cd70結合分子及使用彼之方法
WO2018169922A2 (en) 2017-03-13 2018-09-20 Kite Pharma, Inc. Chimeric antigen receptors for melanoma and uses thereof
EP3490605B1 (en) 2017-04-01 2023-06-07 AVM Biotechnology, LLC Replacement of cytotoxic preconditioning before cellular immunotherapy
SG11201908980PA (en) 2017-04-03 2019-10-30 Kite Pharma Inc Treatment using chimeric receptor t cells incorporating optimized polyfunctional t cells
AU2018257894A1 (en) 2017-04-24 2019-10-31 Kite Pharma, Inc. Humanized antigen-binding domains against CD19 and methods of use
WO2018218105A1 (en) 2017-05-26 2018-11-29 Kite Pharma, Inc. Methods of making and using embryonic mesenchymal progenitor cells
CA3075619A1 (en) 2017-09-15 2019-03-21 Kite Pharma, Inc. Methods and systems for performing a patient-specific immunotherapy procedure with chain-of-custody and chain-of-identity biological sample tracking
WO2019060695A1 (en) 2017-09-22 2019-03-28 Kite Pharma, Inc. CHIMERIC POLYPEPTIDES AND USES THEREOF
MX421741B (es) 2017-10-18 2025-03-14 Kite Pharma Inc Inmunoterapia con receptores de antígeno quimérico y uso de la misma
EP3710471A1 (en) 2017-11-16 2020-09-23 Kite Pharma, Inc. Modified chimeric antigen receptors and methods of use
CA3087481A1 (en) 2018-01-15 2019-07-18 Pfizer Inc. Methods of administering chimeric antigen receptor immunotherapy in combination with 4-1bb agonist
WO2019152957A1 (en) 2018-02-02 2019-08-08 Arizona Board Of Regents On Behalf Of Arizona State University Dna-chimeric antigen receptor t cells for immunotherapy
CA3177757A1 (en) 2018-02-16 2019-08-22 Kite Pharma, Inc. Modified pluripotent stem cells and methods of making and use
TW202322828A (zh) 2018-04-12 2023-06-16 美商凱特製藥公司 利用腫瘤微環境之特性之嵌合受體t細胞治療
JP7174777B2 (ja) 2018-06-01 2022-11-17 カイト ファーマ インコーポレイテッド キメラ抗原受容体t細胞療法
US20210155941A1 (en) 2018-06-22 2021-05-27 Kite Pharma Eu B.V. Compositions and methods for making engineered t cells
IL311860A (en) 2018-08-02 2024-06-01 Kite Pharma Inc Treatment with receptor-antigen chimeric kinetics of T cell expansion and their uses
EP3488851A1 (en) 2018-10-03 2019-05-29 AVM Biotechnology, LLC Immunoablative therapies
EP3632446B3 (en) 2018-10-03 2024-01-24 AVM Biotechnology, LLC Immunoablative therapies
AU2019397033B2 (en) 2018-12-12 2023-06-29 Kite Pharma, Inc. Chimeric antigen receptors and CAR-T cells and methods of use
US20220175900A1 (en) * 2019-04-12 2022-06-09 Cytovac A/S Method for preparation of cancer/testis antigen-specific t-cells
CN118593691A (zh) 2019-05-03 2024-09-06 凯德药业股份有限公司 施用嵌合抗原受体免疫疗法的方法
CN114391021B (zh) 2019-06-21 2026-01-16 凯德药业股份有限公司 TGF-β受体和使用方法
CA3147441A1 (en) 2019-09-03 2021-03-11 Allogene Therapeutics, Inc. Methods of preparing t cells for t cell therapy
IL292665B2 (en) 2019-11-06 2026-02-01 Kite Pharma Inc Chimeric antigen receptor T cell therapy
US20230293530A1 (en) 2020-06-24 2023-09-21 Yeda Research And Development Co. Ltd. Agents for sensitizing solid tumors to treatment
US12551530B2 (en) 2020-08-14 2026-02-17 Kite Pharma, Inc. Immune cell function
US12152251B2 (en) 2020-08-25 2024-11-26 Kite Pharma, Inc. T cells with improved functionality
WO2022093925A1 (en) 2020-10-28 2022-05-05 Kite Pharma, Inc. Flow cytometric method for characterization of t-cell impurities
KR20230124656A (ko) 2020-12-24 2023-08-25 카이트 파마 인코포레이티드 전립선암 키메라 항원 수용체
KR20230129485A (ko) 2021-01-10 2023-09-08 카이트 파마 인코포레이티드 T 세포 요법
US20240076616A1 (en) 2021-01-21 2024-03-07 Cytovac A/S Method for t-cell expansion and related medical applications
TW202241469A (zh) 2021-02-20 2022-11-01 美商凱特製藥公司 免疫療法
EP4305053A1 (en) 2021-03-11 2024-01-17 Kite Pharma, Inc. Improving immune cell function
EP4323943A1 (en) 2021-04-16 2024-02-21 Kite Pharma, Inc. Methods and systems for scheduling a patient-specific immunotherapy procedure
IL307384A (en) 2021-04-16 2023-11-01 Kite Pharma Inc Molecules with a dual link to TACI and BCMA
US12357646B2 (en) 2021-05-14 2025-07-15 Kite Pharma, Inc. Chimeric antigen receptor T cell therapy
CA3221231A1 (en) 2021-05-24 2022-12-01 Kite Pharma, Inc. Chimeric antigen receptor
WO2022261061A1 (en) 2021-06-08 2022-12-15 Kite Pharma, Inc. Gpc3 binding molecules
WO2022269019A1 (en) 2021-06-25 2022-12-29 Cytovac A/S Method for preparation of cytotoxic t lymphocytes with broad tumour-specific reactivity and characteristics of early differentiation cells
WO2023278553A1 (en) 2021-07-01 2023-01-05 Kite Pharma, Inc. Closed-system and method for autologous and allogeneic cell therapy manufacturing
KR20240028503A (ko) 2021-07-02 2024-03-05 카이트 파마 인코포레이티드 세포 요법 응용 분야에 사용되는 유전자 작제물의 유전자 산물에서 변이체를 식별하는 방법
WO2023009989A1 (en) 2021-07-26 2023-02-02 Kite Pharma, Inc. Split chimeric antigen receptors and methods of use
JP7791305B2 (ja) 2021-07-30 2025-12-23 カイト ファーマ インコーポレイテッド 細胞療法により誘発された毒性の監視及び管理
WO2023069936A1 (en) 2021-10-18 2023-04-27 Kite Pharma, Inc. Signaling domains for chimeric antigen receptors
CN118742810A (zh) 2022-02-15 2024-10-01 凯德药业股份有限公司 从免疫疗法预测不良事件
WO2023247324A1 (en) 2022-06-24 2023-12-28 Cytovac A/S Novel combination treatment with adoptive cellular therapy
US20240091261A1 (en) 2022-08-26 2024-03-21 Kite Pharma, Inc. Immune cell function
KR20250097844A (ko) 2022-10-28 2025-06-30 카이트 파마 인코포레이티드 면역요법의 효능 향상 및 지속적인 반응
TW202530421A (zh) 2022-10-28 2025-08-01 美商凱特製藥公司 用於將免疫療法最佳化之因素
KR20250162836A (ko) 2023-03-17 2025-11-19 카이트 파마 인코포레이티드 종양 미세환경이 면역요법의 효능에 미치는 영향
US20250161361A1 (en) 2023-11-01 2025-05-22 Kite Pharma, Inc. Factors for optimizing immunotherapy efficacy
US20250262300A1 (en) 2024-02-16 2025-08-21 Kite Pharma, Inc. Systems, methods, and kits for generating and administering engineered t cells and cd38 targeting compounds as a combination therapy
US20250290154A1 (en) 2024-03-04 2025-09-18 Kite Pharma, Inc. Predictive markers for immunotherapy
WO2025231376A1 (en) 2024-05-03 2025-11-06 Kite Pharma, Inc. Chimeric receptors binding to cll-1 and methods of use thereof
WO2025250819A1 (en) 2024-05-31 2025-12-04 Kite Pharma, Inc. Tricistronic constructs for anti-gpc3 car
US20260009001A1 (en) 2024-07-08 2026-01-08 Kite Pharma, Inc. Systems and methods for applying mechanical force to living cells to generate a phenotypic response
WO2026084968A1 (en) 2024-10-14 2026-04-23 Kite Pharma, Inc. Biomarker based standards and methods of use

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003012085A1 (en) * 2001-07-30 2003-02-13 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Antigen presenting cells, method for their preparation and their use for cancer vaccines

Also Published As

Publication number Publication date
CY1112668T1 (el) 2016-02-10
ATE522600T1 (de) 2011-09-15
US20100092498A1 (en) 2010-04-15
AU2008203730B2 (en) 2013-11-07
DK2102331T3 (da) 2011-10-17
US10023839B2 (en) 2018-07-17
WO2008081035A1 (en) 2008-07-10
AU2008203730A1 (en) 2008-07-10
PT2102331E (pt) 2011-12-19
GB0700058D0 (en) 2007-02-07
HRP20110899T1 (hr) 2011-12-31
EP2102331B1 (en) 2011-08-31
JP2010514455A (ja) 2010-05-06
SI2102331T1 (sl) 2012-01-31
JP5452231B2 (ja) 2014-03-26
US20180036397A1 (en) 2018-02-08
EP2102331A1 (en) 2009-09-23
PL2102331T3 (pl) 2012-01-31

Similar Documents

Publication Publication Date Title
ES2372713T3 (es) Vacuna antitumoral derivada de celulas cd4+ normales modificadas químicamente.
CN100591762C (zh) 抗原呈递细胞、其制备方法及其用于癌症疫苗的用途
EP2700708B1 (en) Enhancing the T-cell stimulatory capacity of human antigen presenting cells in vitro and in vivo and its use in vaccination
CA3127996A1 (en) Pharmaceutical composition for use in the treatment of pancreatic cancer
US11684671B2 (en) Enhancing the T-cell stimulatory capacity of human antigen presenting cells in vitro and in vivo and its use in vaccination
AU2011288416B2 (en) Compositions and methods for producing dendritic cells
US20130129713A1 (en) Method of antigen loading for immunotherapy
CN109983120A (zh) 含有外源线粒体的天然杀伤细胞和含有其的药物组合物
Abraham et al. Gene-modified dendritic cell vaccines for cancer
M. Hofman et al. Immunotherapy of malignant gliomas using autologous and allogeneic tissue cells
Har-Noy et al. Allogeneic CD3/CD28 cross-linked Th1 memory cells provide potent adjuvant effects for active immunotherapy of leukemia/lymphoma
Wang et al. Dendritic cells transduced with a PSMA-encoding adenovirus and cocultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against prostate cancer cells
Vichchatorn et al. Dendritic cells pulsed with total tumor RNA for activation NK-like T cells against glioblastoma multiforme
Izgi et al. Evaluation of two different adjuvants with immunogenic uroplakin 3A-derived peptide for their ability to evoke an immune response in mice
US11090332B2 (en) Antigen specific mRNA cellular cancer vaccines
JP7390740B2 (ja) 腫瘍の治療及び/又は予防のための組成物
Chuntova et al. IMMU-45. CAR-T TREATMENT OF NOVEL MOUSE MODEL OF EGFRVIII+ GBM MIRRORS CLINICAL TRIAL OUTCOMES AND PROVIDES A SYNGENEIC PLATFORM FOR THE INVESTIGATION OF CAR-T MECHANISMS OF ACTION
Beckhove et al. Local tumor growth and spontaneous systemic T cell responses in cancer patients: A paradox and puzzle
Ladomersky et al. IMMU-44. INHIBITING IMMUNOSUPPRESSIVE IDO1 IN ADULTS WITH MALIGNANT GLIOMA–A MOVING TARGET THAT CHANGES WITH TREATMENT, CELL OF ORIGIN, AND AGING
Sousa-Canavez et al. Therapeutic Dendritic Cell Vaccine Preparation Using Tumor RNA Transfection
BRPI0803471A2 (pt) vacina de células hìbridas dendrìticas-tumorais para o tratamento de melanoma