Article Figures & Data
Figures
- FIGURE 1.
Cell line characterization. (A) Flow cytometry analysis of MHC-I (anti–H-2Kb antibody) and TYRP-1/gp75 (TA99 antibody) expression in B16F10 and B16K1 melanoma cells. (B) Radiation sensitivity of 2 cell lines. FITC = fluorescein isothiocyanate.
- FIGURE 2.
In vivo therapeutic efficacy of [225Ac]Ac-DOTA-TA99 mAb (9.25 and 18.5 kBq) in B16F10 cell–bearing C57BL/6J mice (A and B) and athymic and nude mice (C and D). Results are mean ± SEM. *P < 0.05, **P < 0.01, based on log-rank test. NaCl = sodium chloride.
- FIGURE 3.
In vivo therapeutic efficacy of [225Ac]Ac-DOTA-TA99 mAb in B16K1 cell–bearing C57BL/6J mice (A and B) and athymic and nude mice (C and D). Results are mean ± SEM. *P < 0.05, **P < 0.01, based on log-rank test. NaCl = sodium chloride.
- FIGURE 4.
Toxicity of [225Ac]Ac-DOTA-TA99 mAb in immunocompetent mice bearing B16K1 melanoma cell grafts. (A) White blood cell count. (B) Weight measurement in mice after RPT. Results are mean ± SEM. *P < 0.05. **P < 0.01. ***P = 0.0005. NaCl = sodium chloride.
- FIGURE 5.
Biodistribution and dosimetry. (A) Biodistribution of [111In]In-DTPA-TA99 mAb was determined by ex vivo γ-radiation counting of tumor nodules and organs collected at various times (n = 3–4 per time point) after intraperitoneal injection in mice harboring B16F10 and B16K1 tumors (left), with corresponding digital autoradiography images of tumors (delineated by circles) at 48 h after injection (right). (B) Absorbed dose in Gy/kBq was determined for each organ (left), and tumor absorbed dose for [225Ac]Ac-DOTA-TA99 (9.25 kBq) was assessed, with SD (right). Histograms are mean ± SEM. *P < 0.05, based on 2-tailed parametric unpaired t test. **P < 0.01, based on 2-tailed parametric unpaired t test. %IA/g = percentage injected activity per gram of tissue.
- FIGURE 6.
Modulation of MHC-I (H-2Kb) expression on EBRT and RPT. Results are mean ± SD. ****P < 0.0001, based on 2-tailed parametric unpaired t test. IFN-γ is positive control. gMFI = geometric mean fluorescence intensity; NT = not treated.
- FIGURE 7.
MHC-I expression and CD8+ T-cell density in thyroid carcinoma and neuroendocrine tumor samples. Variable patterns of MHC-I immunoreactivity and CD8+ T-cell density are seen. In both tumor types, low MHC-I expression level (patients 1 and 8) was associated with low CD8+ T-cell density (arrows), whereas high MHC-I expression level (patients 2 and 9) was associated with higher CD8 + T-cell density. Scale bars are 50 µm.
Tables
Patient no. Sex Age at surgery (y) Histologic type Localization Grade Stage MHC-I Q score CD8+ T-cell infiltrate 1 M 72 Papillary carcinoma, classic subtype Thyroid NA pT2NxM+x 10 + 2 M 65 Papillary carcinoma, vesicular variant subtype Thyroid NA pT4aN1bM+x 200 +++ 3 M 53 Papillary carcinoma, classic subtype Thyroid NA pT3bN+0M0x 170 ++ 4 F 48 Papillary carcinoma, classic subtype Thyroid NA pT1bN1bM0x 190 ++ 5 F 53 Papillary carcinoma, diffuse sclerosing subtype Thyroid NA pT1(m)N1aM0x 300 +++ 6 F 51 Papillary carcinoma, vesicular variant subtype Thyroid NA pT3(m)NxM+x 0 + 7 M 53 Papillary carcinoma, vesicular variant subtype Thyroid NA pT3aNxM+x 2 + 8 M 63 NET Small intestine 2 pT4N1M1x 1 + 9 M 59 NET Ileum 2 pT4N2M1x 80 ++ 10 F 73 NET Small intestine 2 pT4N1M1 10 + 11 F 73 NET Ileum 2 pT3N1M1 5 + 12 F 58 NET Lymph node metastasis of NET from small intestine 1 pT3N1M1 5 + NA = not applicable; + = weak; ++ = moderate; +++ = strong; NET = neuroendocrine tumor.
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