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176 Immune activation by antigen-specific T cells elicited in patients receiving standard therapy for pediatric solid tumors
  1. Jillian Smith,
  2. Amy Hont and
  3. Catherine Bollard
  1. Children’s National Hospital, Washington, DC, USA


Background Immunotherapy in the form of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells has revolutionized the treatment of select malignancies.1–2 However, beyond CD19+ cancers, clinical responses to CAR-T have been modest in pediatric cancers, likely due to lower mutational burden. Antigen spreading, an expanded anti-tumor immune response through exposure to neoantigens, has been observed in patients following treatment with immunotherapy agents or chemotherapy for malignancies with typically higher mutational burdens.3–6]. However, this has not been observed in pediatric patients with solid tumors after standard treatment. We demonstrated the safety of autologous tumor-associated antigen-specific T lymphocytes (TAA-T) specific for WT1, PRAME, and Survivin in Phase I studies.7 We also identified antigen spreading post-infusion with increased T cells specific for non-targeted antigens MAGE-A3, MAGE-A4, SSX-2, and SOX-2, all expressed on solid tumors.8–12 We hypothesized that antigen spreading would be greater in patients who received TAA-T than in those who received standard chemotherapy or radiation therapy.

Methods Fourteen patients with pediatric solid tumors who received standard-of-care therapy were enrolled on the standard chemotherapy arm and compared to fourteen relapsed/refractory patients who received TAA-T infusion. Peripheral blood samples were taken prior to therapy, during therapy, and off therapy if available, and these were evaluated for the presence of T cells specific to MAGE-A3, MAGE-A4, SSX-2, and SOX-2 as measured by IFN-γ ELISPOT.

Results Our results demonstrate the presence of antigen spreading in newly diagnosed patients who receive standard therapy as evidenced by T cells specific for MAGE-A3 (mean: 28.2, range: 0–137 IFN-y SFC/1e5 cells (SFC)), MAGE-A4 (mean: 31.8, range: 0–270 SFC), SSX-2 (mean: 22.8, range: 0–100 SFC) and SOX-2 (mean: 7.2, range: 0–46 SFC). Similar levels of antigen spreading were also identified in relapsed/refractory patients post TAA-T infusion detecting T cells specific for MAGE-A3 (mean: 30.7, range: 0–249 SFC). MAGE-A4 (mean: 27.6, range: 0–230 SFC), SSX-2 (mean: 33.9, range: 0–200 SFC) and SOX-2 (mean: 39.5, range: 0–270 SFC).

Conclusions These results demonstrate immune activation as evidenced by antigen spreading in newly diagnosed pediatric patients with solid tumors receiving standard-of-care chemotherapy and radiation therapy, the majority of which remain in remission following treatment. Similar levels of antigen spreading were also observed in responding patients who received TAA-T for relapsed/refractory disease. This data provides further support for the role of immunotherapy in the treatment of pediatric solid tumors and the strong anti-tumor response these therapies can potentiate.


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