What question did this study set out to answer?

To evaluate the safety, tolerability, and immunogenicity of sequential cancer vaccines targeting tumor-associated and personalized neoantigens in uLMS.

March 7, 2026

Abstract LB-B009: Design and immunogenicity of sequential cancer vaccination targeting shared tumor-associated antigens and personalized neoantigens in a single patient with uterine leiomyosarcoma

Key Points

To evaluate the safety, tolerability, and immunogenicity of sequential cancer vaccines targeting tumor-associated and personalized neoantigens in uLMS.
Administered cancer vaccines to a 54-year-old female with uLMS after resection.
Delivered Montanide-adjuvanted peptide vaccines targeting shared tumor-associated antigens over multiple doses.
Subsequently, provided personalized peptide vaccines with recombinant Flt3 agonist in two series, focusing on neoantigens derived from SNVs and SVs.
Monitored T cell responses via ELISPOT and flow cytometry by collecting peripheral blood samples longitudinally.
Vaccines were well tolerated with grade 1-2 adverse events, including injection site reactions.
Immune responses included CD8+ and CD4+ T cells, with notable immunogenicity seen in specific peptide doses.
2 out of 19 peptides and 15 out of 30 from the shared TAA vaccines were immunogenic, while 11 out of 12 from PGV001 were also immunogenic.

Abstract

Abstract INTRODUCTION: Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer. Standard of care involves complete resection and chemotherapy. However, recurrence rates remain high and treatment options after relapse are limited, underscoring the need for improved adjuvant therapies. Cancer vaccines are a promising strategy that induce antitumor immunity and correlate with better clinical outcomes. However, optimal antigen selection, combinations and delivery strategies, are poorly defined, especially for rare cancers. OBJECTIVES: This study was conducted to assess the safety, tolerability and immunogenicity of sequentially delivered cancer vaccination targeting tumor-associated antigens (TAA) and personalized neoantigens derived from single nucleotide variants (SNVs) and structural variants (SVs) in uLMS in the adjuvant setting. METHODS: A 54-year-old female patient with resected uLMS was treated with a series of cancer vaccines. Initially, Aug-Dec 2024, the patient received 6 doses of Montanide-adjuvanted peptide vaccines targeting shared TAAs, administered at ∼3-week intervals. The first 3 doses included 19 short peptides; the last 3 included 30 short and long peptides. Subsequently, the patient received two personalized peptide vaccines, PGV001 and 002, in combination with recombinant Flt3 agonist, CDX-301, during Feb-May and Sep-Dec 2025, respectively. Each vaccine was administered in 4 doses at ∼4-week intervals and contained long peptides. PGV001 included 12 peptides targeting neoantigens primarily derived from SNVs and predicted to strongly bind to patient’s HLA-I alleles. PGV002 included 8 peptides in the first dose; 17 peptides in the subsequent doses, targeting neoantigens derived from SVs, including epitopes validated by mass spectrometry. Tetanus helper peptide, Poly-ICLC, and Montanide were included in each dose, except Montanide was replaced with saline for the last 3 doses of PGV002. Peripheral blood samples were collected longitudinally. Vaccine-induced T cell responses were evaluated by measuring antigen-specific effector cytokine production by ex vivo ELISPOT and intracellular staining by flow. RESULTS: The vaccines were tolerated well with grade 1-2 adverse events, primarily injection site reactions. Following the first PGV002 dose, the patient experienced grade 2 flu-like symptoms and localized erythema and swelling, attributed to Montanide. The TAA and PGV001 vaccines elicited both CD8+ and CD4+ T cell responses. 2/19 and 15/30 peptides from early and late TAA doses, respectively, and 11/12 of PGV001 peptides were immunogenic. Immunogenicity of PGV002 is currently under investigation. CONCLUSION: Sequential administration of peptide-based vaccines was safe, feasible, well tolerated. Each vaccine elicited robust T cell responses, pre-existing and de novo, against distinct antigens, iteratively broadening immune coverage. Although evaluated in a single patient, this strategy offers a framework for tailoring immunotherapy in rare, aggressive cancers where treatment cannot be delayed for personalized vaccine development. Citation Format: Mansi Saxena, Cansu Cimen Bozkus, Anna Kaminska, Leandra Velazquez, Mesude Bicak, Denise Rodriguez, Daniela Delbeau-Zagelbaum, John Connolly, Alireza Samiei, EnJun Yang, Jeffrey Tsao, William J. Gibson, Dirk Jäger, Philip Friedlander, Nina Bhardwaj. Design and immunogenicity of sequential cancer vaccination targeting shared tumor-associated antigens and personalized neoantigens in a single patient with uterine leiomyosarcoma abstract. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr LB-B009.

AI से पूछें

Bookmark