VACCINE STUDIES TARGETING MELANOMA

Öz

Melanoma is a malignancy of melanocytic origin that has particular importance among skin cancers due to its high metastatic potential and mortality. Although surgery, chemotherapy, radiotherapy, and targeted therapies achieve partial success in melanoma, treatment resistance, relapse, and systemic adverse effects highlight the ongoing need for novel immunotherapeutic approaches. Cancer vaccines have emerged as strategies that aim to reduce tumor burden and prevent recurrence by inducing specific humoral and cellular immune responses against tumor cells or tumor-associated antigens. In this review, the current status of vaccine studies targeting the immune system in the treatment of melanoma is comprehensively evaluated within the framework of mRNA-based vaccines, dendritic cell (DC) vaccines, and neoantigen-based personalized vaccine strategies. Preclinical animal models and clinical studies involving patients with metastatic melanoma reported in the literature demonstrate that mRNA and DC vaccines can effectively activate CD4⁺ and CD8⁺ T cells, slow tumor growth, and provide clinical responses in selected cases. However, the genetic heterogeneity of melanoma, immune escape mechanisms, appropriate antigen selection, optimization of adjuvants and delivery systems, and issues related to manufacturing and cost constitute major limitations. Current evidence indicates that melanoma vaccines, particularly when combined with other immunotherapies such as immune checkpoint inhibitors, have the potential to contribute meaningfully to treatment; however, well-designed clinical trials involving larger patient cohorts are needed before these approaches can be incorporated into routine clinical practice.

Anahtar Kelimeler

• Melanoma
• cancer vaccines
• mRNA vaccines
• dendritic cell vaccines
• immunotherapy

MELANOMA KANSERİNE KARŞI GELİŞTİRİLEN AŞI ÇALIŞMALARI

Öz

Melanom; melanosit kökenli, yüksek metastatik potansiyeli ve mortalitesi nedeniyle deri kanserleri arasında özel öneme sahip bir malignitedir. Cerrahi, kemoterapi, radyoterapi ve hedefe yönelik tedaviler melanomda kısmi bir başarı sağlasa da tedavi direnci, nüks ve sistemik yan etkiler nedeni ile yeni immünoterapötik yaklaşımlara ihtiyaç devam etmektedir. Kanser aşıları; tümör hücrelerine veya tümörle ilişkili antijenlere karşı özgül humoral ve hücresel immün yanıt oluşturarak tümör yükünü azaltmayı ve nüksü önlemeyi amaçlayan stratejiler olarak öne çıkmaktadır. Bu derlemede, melanom tedavisinde bağışıklık sistemini hedefleyen aşı çalışmalarının güncel durumu; mRNA tabanlı aşılar, dendritik hücre (DC) aşıları ve neoantijen temelli kişiselleştirilmiş aşı stratejileri çerçevesinde kapsamlı olarak incelenmiştir. Literatürde yer alan preklinik hayvan modelleri ve metastatik melanom hastalarını içeren klinik çalışmalar, mRNA ve DC aşılarının CD4⁺ ve CD8⁺ T hücrelerini etkin şekilde aktive edebildiğini, tümör büyümesini yavaşlatabildiğini ve seçilmiş olgularda klinik yanıt sağlayabildiğini göstermektedir. Bununla birlikte, melanomun genetik heterojenliği, immün kaçış mekanizmaları, uygun antijen seçimi, adjuvan ve taşıyıcı sistemlerin optimizasyonu ile üretim ve maliyet süreçleri önemli kısıtlılıklar oluşturmaktadır. Mevcut veriler, melanoma aşılarının özellikle immün kontrol noktası inhibitörleri gibi diğer immünoterapilerle kombine edildiğinde tedaviye anlamlı katkı sağlayabilecek potansiyele sahip olduğunu, ancak bu yaklaşımların rutin klinik kullanıma girebilmesi için daha geniş hasta serilerini içeren, iyi tasarlanmış klinik çalışmalara ihtiyaç bulunduğunu ortaya koymaktadır.

Anahtar Kelimeler

• Melanom
• kanser aşıları
• mRNA aşıları
• dendritik hücre aşıları
• immünoterapi

Kaynakça

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