Results: 5

1.
Fig. 5

Fig. 5. From: Lymph Node-Targeted Immunotherapy Mediates Potent Immunity Resulting in Regression of Isolated or Metastatic HPV-Transformed Tumors.

Control of pulmonary metastases by intra-lymph node immunization with E7 peptide and pI:C. Mice were injected intravenously with 5 × 105 C3.43 tumor cells and then immunized with one of the following intranodal E7 + pI:C vaccine time courses: day 1, 4, 15, and 20 (A); day 8, 12, 22, and 26 (B); or day 15, 20, 29, and 33 (C). Survival curves for each group (A, B, C) are shown and the outcome for E7 + pI:C immunized mice (n = 9) was compared to pI:C only (n = 9) and untreated tumor control mice (n=9). Log-Rank statistical tests confirmed that survival in the E7 + pI:C group for each vaccine time course (A, B and C) was significantly longer than survival in the tumor control group (p = to 0.0007, 0.001, and 0.032 respectively) and the pI:C only group when immunization began on day 1 (A, p = 0.006) and day 8 (B, p = 0.004) but not day 15 (C, p = 0.06).

Kent A. Smith, et al. Clin Cancer Res. ;15(19):6167-6176.
2.
Fig. 1

Fig. 1. From: Lymph Node-Targeted Immunotherapy Mediates Potent Immunity Resulting in Regression of Isolated or Metastatic HPV-Transformed Tumors.

Intra-lymph node immunization with E7 peptide and pI:C elicits robust immunity protective against tumor challenge. Flow cytometry dot plots (A) comparing the tetramer response from an immunized (E7 + pI:C) and naïve control mouse representative of data shown in (B). The results are expressed as the frequency of E7 tetramer+ CD8+ T cells relative to the total CD8+ T cell population measured in peripheral blood 10 days after the completion of the immunization protocol. Intra-lymphatic vaccination with E7 49-57 HPV antigen and pI:C resulted in substantial E7-specific CD8+ T cell responses, whereas pI:C or E7 49-57 peptide alone had no significant impact on immune response when compared to tumor control or naïve mice (B). The mean E7 tetramer response +/- SEM for each group is shown (n=10). HPV 16 E7 49-57 antigen-specific immune response correlated with tumor protection (C). Immunization of mice with E7 49-57 peptide and pI:C (n=20) resulted in complete protection from subcutaneous challenge with 105 HPV transformed C3.43 tumor cells as compared to tumor control mice (n=20) and 90% protection following a tumor re-challenge compared to second group of tumor control mice (n=3).

Kent A. Smith, et al. Clin Cancer Res. ;15(19):6167-6176.
3.
Fig. 2

Fig. 2. From: Lymph Node-Targeted Immunotherapy Mediates Potent Immunity Resulting in Regression of Isolated or Metastatic HPV-Transformed Tumors.

Intra-lymph node immunization with E7 peptide and pI:C mediates immunological regression of solid tumor. In a therapeutic model of HPV 16, the anti-tumor efficacy of intranodal versus subcutaneous (SC) dosing was compared. C57BL/6 mice were challenged SC with 105 C3.43 HPV tumor cells on day 0 and then immunized with a mixture of E7 49-57 peptide and pI:C in each bilateral inguinal lymph node (n=19) or an equivalent amount of vaccine SC (n=19) on day 7, 10, 21, and 24. The immune response was measured by E7 49-57 tetramer staining on day 31 from peripheral blood (A) and tumor size for each group was calculated and compared to untreated tumor challenged control (n=19) mice (B). Lymph node immunized mice generated statistically significant E7 49-57 specific immune responses with an average of 14.5% tetramer positive CD8+ T cells (A) compared to SC dosed mice (p < 0.0001). In addition, tumors in mice immunized in the lymph node began to regress on day 15 resulting in 84% of animals in remission at day 40 (B). This response was significantly superior to animals dosed SC (p < 0.003) whose tumor progression was only delayed compared to tumor controls but resulted in 32% of animals in disease remission. Untreated tumor control mice displayed background levels of E7 tetramer staining (A) and their tumors progressed exponentially without regression as expected (B). Log-rank statistical tests confirmed that survival in the E7 + pI:C group was significantly prolonged when compared to animals immunized SC (p = 0.0004) or when compared to tumor controls (p = 0.0001) (C).

Kent A. Smith, et al. Clin Cancer Res. ;15(19):6167-6176.
4.
Fig. 4

Fig. 4. From: Lymph Node-Targeted Immunotherapy Mediates Potent Immunity Resulting in Regression of Isolated or Metastatic HPV-Transformed Tumors.

Adjunctive therapy with CTX enables immunotherapy in a more advanced disease setting. Mice were inoculated with 105 HPV-16 transformed C3.43 tumor cells on day 0, treated with CTX on Day 14 and 18 (n=20), immunized with E7 49-57 HPV peptide and pI:C in bilateral inguinal lymph nodes on day 20, 24, 34, and 38 (n=20), or treated with CTX then E7 + pI:C immunotherapy (n=20). Immune response (A) and tumor progression (B) was compared to untreated tumor control mice (n=20). The immune response following immunotherapy was measured by E7 49-57 tetramer staining on day 45 from peripheral blood. The immunized only group (E7 + pI:C) displayed HPV specific immune responses in the range of 20% with no observed inhibition of immune response in animals treated with CTX + E7 + pI:C which generated a similar tetramer response. The naïve control (n=5) and CTX control groups generated background levels of tetramer staining (A). CTX + E7 + pI:C induced significant tumor regression (p < 0.001) compared to E7 + pI:C immunotherapy alone, CTX alone, and untreated tumor controls (B). Evaluation of adjunctive therapy on animal survival (C). A second therapeutic cycle was administered with animals receiving CTX on day 46 and 50 (n=20), lymph node immunization with E7 + pI:C on day 52, 56, 65, and 69 (n=20), or treated with CTX + E7 + pI:C (n=20). Grey arrows indicate CTX treatment and black arrows indicate immunization days. Log-Rank statistical tests confirmed that survival in the CTX + E7 + pI:C group was significantly longer than survival in the control group (p < 0.0001, n=20), the CTX only group (p = 0.0188) and the E7 + pI:C immunotherapy only group (p = 0.0033).

Kent A. Smith, et al. Clin Cancer Res. ;15(19):6167-6176.
5.
Fig. 3

Fig. 3. From: Lymph Node-Targeted Immunotherapy Mediates Potent Immunity Resulting in Regression of Isolated or Metastatic HPV-Transformed Tumors.

CD4+/CD25+/FoxP3HI Tregs impair in situ function of TILs in advanced tumors and are reduced following CTX treatment. Mice were inoculated with 105 HPV-16 transformed C3.43 tumor cells on day 0 and immunized with E7 49-57 HPV peptide and pI:C in bilateral inguinal lymph nodes on day 20, 24, 34, and 38 (n=3). Immunization control mice received PBS + pI:C in bilateral inguinal lymph nodes on day 20, 24, 34, and 38 (n=3). (A) Flow cytometry dot plots comparing the frequency (top panel) and the functional ability to produce IFN-γ (bottom panel) of E7 49-57 antigen-specific TILs from representative E7 + pI:C immunized or tumor control (PBS + pI:C) mice. (B) Impaired in situ function of TILs measured by in vivo cytotoxicity assay. E7 + pI:C immunized mice with progressing tumors cleared greater than 90% of HPV 16 E7 49-57 labelled target cells in spleen whereas TILs from the same mice had little cytotoxic effect on target cells within established tumors. CTX treatment (100 mg/kg, IP) in a second group of E7 + pI:C immunized mice (n=3) with progressive disease resulted in enhanced killing of specific target cells in tumors (p = 0.03) and had no adverse effect on target cell lysis in spleen. (C) Immunized mice bearing HPV-16 transformed tumors (n=3) displayed approximately three fold higher numbers of CD4+/CD25+/FoxP3+ Tregs in spleen compared to naïve mice (n=3) or immunized mice whose tumors completely regressed (n=3). The level of CD4+/CD25+/FoxP3+ Tregs could be reduced in the spleen (C, n=3) and the levels of CD4+ and CD4+/CD25+/FoxP3+ cells could be reduced in tumor (D) of mice with progressive disease by a single intraperitoneal injection of 100 mg/kg CTX (n=3 mice / group).

Kent A. Smith, et al. Clin Cancer Res. ;15(19):6167-6176.

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Write to the Help Desk