# Harnessing Vaccines in the Treatment of Solid Tumors: Advances, Challenges, and Future Directions

**Authors:** Jorge Iranzo, Edoardo Giordano, Renato Maria Marsicano, Dario Trapani, Antonio Marra, Carmen Belli, Paola Zagami, Pier Paolo Maria Berton Giachetti, Emanuela Ferraro, Ida Minchella, Edoardo Crimini, Giuseppe Curigliano

PMC · DOI: 10.3390/vaccines14020135 · Vaccines · 2026-01-29

## TL;DR

This review discusses the potential of vaccines in treating solid tumors, highlighting recent advances, challenges, and future directions in cancer immunotherapy.

## Contribution

The paper provides a comprehensive overview of current vaccine development and clinical outcomes in solid tumor treatment.

## Key findings

- Immunotherapy has shown durable responses and safety across various tumor types.
- Sipuleucel-T is the only FDA-approved cell-based vaccine for solid tumors.
- Personalized neoantigen and mRNA vaccines show promise in early trials.

## Abstract

Immunotherapy has become a cornerstone of cancer treatment in both the early and advanced setting in recent years, leading to the achievement of substantial and durable responses with an excellent safety profile across different tumor types. This demonstrates the high potential of engaging the immune system in the treatment of solid tumors. Consequently, there has been renewed interest in vaccines to enhance therapeutic effects, prevent tumor development, and eliminate or control minimal residual disease. Although therapeutic cancer vaccines have shown potential benefits in certain settings, their results in clinical trials remain highly variable and generally unsatisfactory, depending on tumor site, biology, and vaccine type. Currently, Sipuleucel-T for prostate cancer is the only cell-based vaccine that received FDA approval for the treatment of a solid tumor. Innovative techniques such as personalized neoantigen vaccines and mRNA-based vaccines have shown promising preclinical and early-phase clinical results, supporting their further development. Despite the current evidence of vaccine efficacy in treating solid tumors being derived from only a few clinical trials with relatively small sample sizes, ongoing trials are also exploring innovative approaches aimed at preventing cancer development or enhancing immune responses in combination with other immunotherapeutic agents. In this review, we provide an overview of the clinical results and the current state of vaccine development for cancer treatment, outlining future perspectives on their role in managing patients with cancer.

## Linked entities

- **Diseases:** cancer (MONDO:0004992), prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255], EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, KIF20A (kinesin family member 20A) [NCBI Gene 10112] {aka MKLP2, RAB6KIFL, RCM6}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, MAGEA3 (MAGE family member A3) [NCBI Gene 4102] {aka CT1.3, HIP8, HYPD, MAGE3}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, KLK3 (kallikrein related peptidase 3) [NCBI Gene 354] {aka APS, KLK2A1, PSA, hK3}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, PMEL (premelanosome protein) [NCBI Gene 6490] {aka D12S53E, HMB-45, HMB45, ME20, ME20-M, ME20M}, MSLN (mesothelin) [NCBI Gene 10232] {aka MPF, SMRP}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, PDAP1 (PDGFA associated protein 1) [NCBI Gene 11333] {aka HASPP28, PAP, PAP1}, FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321] {aka FLT, FLT-1, VEGFR-1, VEGFR1}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, WT1 (WT1 transcription factor) [NCBI Gene 7490] {aka AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1}, LALBA (lactalbumin alpha) [NCBI Gene 3906] {aka HAMLET, LYZG}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, LAG3 (lymphocyte activating 3) [NCBI Gene 3902] {aka CD223}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, HAVCR2 (hepatitis A virus cellular receptor 2) [NCBI Gene 84868] {aka CD366, HAVcr-2, KIM-3, SPTCL, TIM3, TIMD-3}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, ACP3 (acid phosphatase 3) [NCBI Gene 55] {aka 5'-NT, ACP-3, ACPP, TM-PAP}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}
- **Diseases:** castration-resistant prostate cancer (MESH:D064129), TNBC (MESH:D064726), Breast Cancer (MESH:D001943), neurological symptoms (MESH:D009461), NSCLC (MESH:D002289), GBM (MESH:D005909), bladder cancer (MESH:D001749), solid (MESH:D018250), infectious diseases (MESH:D003141), Prostate Carcinoma (MESH:D011472), inflammatory (MESH:D007249), injury to (MESH:D014947), TAAs (MESH:C535887), gliomas (MESH:D005910), Melanoma (MESH:D008545), Prostate Cancer (MESH:D011471), precancerous (MESH:D011230), Pancreatic Adenocarcinoma (MESH:D010190), Lung cancer (MESH:D008175), Cancer (MESH:D009369), COVID-19 (MESH:D000086382), toxicity (MESH:D064420), Metastatic (MESH:D000092182)
- **Chemicals:** zolbetuximab (MESH:C585662), testosterone (MESH:D013739), lipid (MESH:D008055), Atezolizumab (MESH:C000594389), QS-21 (MESH:C078785), FOLFIRINOX (MESH:C000627770), Ipilimumab (MESH:D000074324), gemcitabine (MESH:D000093542), nivolumab (MESH:D000077594), bevacizumab (MESH:D000068258), lipid A (MESH:D008050), saponin (MESH:D012503), cyclophosphamide (MESH:D003520), platinum (MESH:D010984), AS15 (-), CpG 7909 (MESH:C483020), Radium-223 (MESH:C000615150), uridine (MESH:D014529), temozolomide (MESH:D000077204), pembrolizumab (MESH:C582435), trastuzumab (MESH:D000068878)
- **Species:** Hepatitis B virus (no rank) [taxon 10407], Listeria monocytogenes (species) [taxon 1639], Adenoviridae (family) [taxon 10508], Human papillomavirus (species) [taxon 10566], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** NEO-PV-01 — Homo sapiens (Human), Embryonic stem cell (CVCL_XJ48)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12944923/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944923/full.md

## References

140 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944923/full.md

---
Source: https://tomesphere.com/paper/PMC12944923