Personalized Cancer Vaccines in the Clinical Trial Pipeline.

1
Introduction
The development of personalized cancer vaccines, tailored to a patient's tumor antigens, has emerged as a promising strategy in targeted cancer immunotherapy [1]. Unlike traditional therapies, personalized vaccines target tumor‐specific mutations in individual patients, offering the potential for improved efficacy and reduced off‐target effects [2].
In recent years, the development of personalized cancer vaccines has gained significant momentum, with numerous clinical trials exploring diverse vaccine platforms, including peptide‐based, RNA‐based, DNA‐based, and dendritic cell‐based approaches. This article provides an overview of the current clinical trial landscape for personalized cancer vaccines, highlighting trends, geographic distribution, sponsors, and vaccine platforms, as captured in the ClinicalTrials.gov database.

2
Materials and Methods
Clinical trial data were downloaded from ClinicalTrials.gov on November 25, 2024, using the following search criteria:
Condition: Cancer

Intervention/treatment: Personalized vaccine

Study type: Interventional

Phase: Early Phase 1, Phase 1, Phase 2, Phase 3

Status parameter: “Recruiting,” “Not yet recruiting,” “Active, not recruiting,” “Enrolling by invitation,” or “Completed.”

In our analysis, trials designated as “Early Phase 1” were grouped with Phase 1 trials. “Phase 1/Phase 2” trials were also combined with Phase 1 trials, while “Phase 2/Phase 3” trials were merged with Phase 2 trials.
Clinical trial statuses of “Recruiting,” “Not yet recruiting,” “Active, not recruiting,” and “Enrolling by invitation” were collectively categorized as “Active.” For clinical trial NCT03929029, which has published results on ClinicalTrials.gov, the status was considered “Completed.”
As of November 25, 2024, we identified 79 interventional clinical trials that met our search criteria. One trial evaluating a pneumococcal 13‐valent conjugate vaccine was excluded as it was unrelated to the study focus.
Study details for each clinical trial were analyzed, including the type of vaccine and details on the conditions. Detailed clinical trial data are provided in Supporting Information File S1.
Cancer types were grouped according to the location of the cancer. The categories applied to the analysis are:
“Brain Cancer”—Glioblastoma, Gliomas, Pediatric Brain Tumor, Childhood Glioblastoma

“Breast Cancer”—Breast Cancer, Triple Negative Breast Cancer

“Pancreatic Cancer”—Pancreatic Tumor, Pancreatic Adenocarcinoma

“Hematologic Malignancies”—Lymphocytic Leukemia, Follicular Lymphoma, Smoldering Plasma Cell Myeloma

“Lung Cancer”—Non‐small Cell Lung Cancer, Small Cell Lung Cancer, Squamous Cell Lung Cancer, Squamous Non‐small Cell Lung Cancer

“Melanoma”—Melanoma, Cutaneous Melanoma

“Prostate Cancer”—Prostate Cancer

“Digestive System Cancers”—Colorectal Neoplasms, Esophageal Cancer, Hepatocellular Carcinoma, Digestive System Neoplasms

“Bladder Cancer”—Bladder Cancer, Urothelial Cancer

“Kidney Cancer”—Kidney Cancer

“Head and Neck Cancer”—Head and Neck Cancer, Squamous Cell Carcinoma of the Head and Neck

“Ovarian Cancer”—Ovarian Carcinoma, Epithelial Ovarian Cancer

“Sarcoma”—Ewing Sarcoma, Rhabdomyosarcoma, Synovial Sarcoma

“Solid Tumors”—Three or more different types of solid tumors investigated in one clinical trial

“Neoplasms (Unspecified)”—Neoplasms

Neoantigen vaccines were divided into 7 different categories: Cell vaccine, RNA vaccine, DNA vaccine, Yeast vaccine, Peptide vaccine, Dendritic cell vaccine, and Unspecified.
For trials classified as “Completed,” publications associated with their respective NCT numbers were reviewed to extract details on safety, immunogenicity, and efficacy outcomes.

3
Results
As of November 25, 2024, a total of 78 personalized cancer vaccine trials on ClinicalTrials.gov met our selection criteria. Of these, 70 were in Phase 1, with 50 active and 20 completed. In Phase 2, there were 8 trials, with 6 active and 2 completed. This dataset does not represent a complete list of trials during this period, as some clinical studies may not be registered on ClinicalTrials.gov.
The distribution of vaccine platforms is summarized in Figure 1. As of November 25, 2024, peptide vaccines were the most common, with 31 trials, followed by dendritic cell vaccines (15 trials) and RNA vaccines (13 trials). Nine trials were categorized as unspecified. DNA vaccines accounted for 6 trials, while cell‐based vaccines were reported in 3 cases. Yeast vaccines were the least represented, with a single occurrence.
Further classification of trials based on conditions, sponsors, and geographical locations is shown in Figure 2 and summarized in Supporting Information File S1.
Solid tumors were the most commonly targeted condition, with 16 trials in Phase 1 and 1 in Phase 2 studies. Brain cancer followed with 12 Phase 1 trials. Pancreatic cancer accounted for 10 Phase 1 trials, and breast cancer included 8 Phase 1 and 1 Phase 2 trials. Other cancers, such as digestive system cancers, melanoma, and hematologic malignancies, had 4 Phase 1 trials each, with varying representation in Phase 2. Less commonly targeted cancers included lung, bladder, and ovarian cancers.
Among 78 trials, industry sponsors conducted 17 studies. Gritstone Bio performed 3 trials, followed by Instituto de Medicina Regenerativa, BioNTech, and Mirror Biologics, each with 2 trials. Other sponsors, such as ModernaTX and Nykode Therapeutics ASA, contributed 1 trial each. Academic or non‐profit funding supported 61 trials. Washington University School of Medicine was the leading sponsor with 6 trials, followed by Dana‐Farber Cancer Institute with 5 trials. Several institutions, including Sir Run Run Shaw Hospital, Ruijin Hospital, and Universidad Nacional de Colombia, conducted 3 trials each.
The majority of trials were conducted in the United States (34 trials), followed by China with 19 trials. Further down the list are Colombia, Thailand, and Germany, with 3 trials each. Mexico and Switzerland each hosted 2 trials. Some trials were conducted across multiple countries, including the United States and Australia (2 trials).
Enrollment sizes varied widely, ranging from small exploratory cohorts of fewer than 10 participants to larger‐scale trials enrolling up to 700 patients. The majority of trials (66) had fewer than 50 participants and only 4 trials aimed to enroll more than 100 patients.
The publications associated with NCT numbers for completed clinical trials were further investigated. The results of these trials are summarized in Table 1.

4
Discussion
This report provides an overview of personalized cancer vaccines registered on ClinicalTrials.gov as of November 25, 2024. A total of 78 trials were identified, with 70 in Phase 1 and 8 in Phase 2, highlighting the early stages of the clinical development process. Among these, 56 trials are currently active, while 22 have been completed, reflecting the ongoing exploration of personalized vaccine approaches in oncology.
Our analysis showed that peptide vaccines were the most frequently tested modality, with 31 trials, followed by dendritic cell vaccines (15 trials) and RNA vaccines (13 trials). Other vaccine types, such as DNA, cell‐based, and yeast vaccines, were less represented.
Most peptide vaccines focus on epitope peptides that activate CD8+ T cells or CD4+ T helper cells, targeting tumor‐associated or tumor‐specific antigens [16]. For example, personalized cancer vaccines based on synthetic long peptides (25–30 amino acids in length) are designed to elicit immune responses against cancer neoantigens (NCT05741242, NCT06529822). Peptide vaccines are sometimes evaluated in combination with immune adjuvants, such as poly‐ICLC, to enhance immune readiness by activating TLR3 and associated pathways (NCT06614140). Granulocyte‐macrophage colony‐stimulating factor is another commonly used adjuvant (NCT05475106). Additionally, checkpoint inhibitors (e.g., anti‐PD‐1, anti‐PD‐L1, or anti‐CTLA4) are included in some clinical trials to prevent immune exhaustion and sustain a robust immune response (NCT06614140). Patient‐specific cancer vaccines are developed through next‐generation whole‐exome sequencing of tumor and normal tissue, as well as RNA sequencing of the tumor, to identify tumor‐specific mutations. Based on these findings, a custom peptide vaccine is formulated to target neoantigens (NCT06094101, NCT06614140).
Dendritic cell vaccines stimulate specific immune reactions capable of precisely targeting and eliminating selected cells [17]. Different types of dendric cell vaccines are in development, including peptides loaded autologous (NCT04105582, NCT05714306, NCT04627246, NCT06253234), tumor‐lysate loaded (NCT03879512, NCT05714306), and mRNA tumor antigen pulsed dendritic cell vaccines (NCT02808364). In some clinical trials, regulatory T cells are depleted through a short course of metronomic cyclophosphamide prior to vaccine administration to enhance immune response induction (NCT03879512). Dendritic cell vaccines are typically investigated in combination with anti‐PD‐L1, anti‐CTLA4, or anti‐VEGF during the post‐vaccine phase and maintenance period to enhance the efficacy of primed T‐cell responses (NCT03879512, NCT05767684, NCT04627246).
RNA vaccines have emerged as a cost‐effective approach for developing neoantigen‐based cancer vaccines [18]. Different formulations are under development, including naked RNA vaccines (NCT02035956, NCT06685653) and RNA lipid particle vaccines (NCT06389591). RNA vaccines are frequently investigated in combination with checkpoint inhibitors to enhance their therapeutic efficacy (NCT06156267, NCT03897881, NCT04161755, NCT05916261).
Of the registered trials covered in this analysis, 16 Phase 1 trials targeted solid tumors. These trials investigated unspecified solid tumors or included three or more different tumor types. Brain cancer was analyzed in 12 trials, with the majority enrolling patients with glioblastoma, the most aggressive type of brain cancer. These trials included studies on newly diagnosed glioblastoma (NCT03223103, NCT02709616, NCT02149225, NCT04015700, NCT05743595), recurrent glioblastoma (NCT02808364, NCT06389591), and childhood glioblastoma (NCT03879512). Given the limited treatment options for glioblastoma, new effective therapies are needed for these patients [19]. Ten trials focused on pancreatic cancer. Standard‐of‐care treatments for pancreatic patients often face challenges due to resistance, underscoring the need for personalized and precise therapeutic approaches [20]. Breast cancer was investigated in 8 Phase 1 and 1 Phase 2 trials. Seven of these studies enrolled patients with triple‐negative breast cancer, the most aggressive form of breast cancer, which is typically associated with a poorer survival rate compared to other subtypes [21].
Sponsorship data indicate that the majority of trials (61 out of 78) were funded by academic institutions or nonprofit organizations, highlighting the critical role of academic research in advancing cancer vaccine development. Industry sponsors backed 22% of studies, with companies such as Gritstone Bio, Instituto de Medicina Regenerativa, BioNTech, and Mirror Biologics sponsoring multiple trials.
Geographically, the United States leads in the number of trials (34 studies). China follows with 19 trials, while several other countries, including Colombia, Thailand, and Germany, have made notable contributions. The multinational nature of these trials underscores the global interest in personalized cancer vaccines.
Completed clinical trials evaluated various personalized neoantigen vaccines across different cancer types, focusing on safety, immunogenicity, and clinical responses. Across these studies, vaccines were generally well‐tolerated, with mild adverse events such as injection site reactions, fatigue, and fever. Strong immune responses were observed, with many patients developing T‐cell responses against neoantigens. Some trials reported objective responses, such as tumor shrinkage or prolonged progression‐free survival, particularly in melanoma, glioblastoma, and urothelial cancer. While no trial demonstrated a universal cure, several showed promising signs of activity, and immune responses persisted in some cases for extended periods.
While this analysis provides insights into the ongoing efforts to develop personalized cancer vaccines, it is important to note that this dataset is not exhaustive. Many trials, particularly those not registered on ClinicalTrials.gov, may not be captured here. Additionally, the data presented only reflect trials registered up until November 25, 2024, and ongoing studies or trials that have recently commenced may not be included.
In conclusion, the landscape of cancer personalized vaccine trials is expanding, with a diverse array of vaccine types under investigation, a strong emphasis on solid tumors, and substantial involvement from both academic and industry sponsors. As these trials progress, further data on the safety, efficacy, and long‐term outcomes of personalized vaccines will be crucial in determining their potential to revolutionize cancer treatment.

Author Contributions
Both authors had contributed to all the stages in the preparation of this manuscript for publication.

Conflicts of Interest
The authors declare no conflicts of interest.

Supporting information

Supplementary File 1: ajco70006‐sup‐0001‐SuppMat‐File1.xlsx