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Table 2 Studies that investigated the effects of combining radiofrequency ablation with immunomodulation and their results

From: Immuno-thermal ablations – boosting the anticancer immune response

Radiofrequency Ablation and Immunotherapy

Reference

Tumor Model

Immunotherapy

Endpoints

RFA Monotherapy

Combination Therapy

Behm, B., et al. [31]

VX2 Rabbit Liver Cancer

CpG B

Mean Animal Survival After Inoculation

97.3 Days

(Range: 76–120)

(p < 0.05 versus Control)

113.9 Days

(Range: 89–120)

(p < 0.05 versus Control & Monotherapy)

Tumor Specific Lymphocyte Stimulation Index 2 Weeks After Treatment

88.49 SI

(39.30 StdDev)

(p < 0.05 versus Control)

103.43 SI

(55.55 StdDev)

(p < 0.05 versus Control)

Cytolytic Activity 2 Weeks After TreatmentNS

487.79 RLU

(148.69 StdDev)

(Not Significant versus Control)

972.72 RLU

(362.77 StdDev)

(p < 0.05 versus Control)

Rechallenge With Malignant Cells to Animals Surviving 160 Days

All Animals Developed Pulmonary Metastases

Pulmonary Metastases Developed in 2 out of 6 Animals

den Brok, M.H., et al. [10]

B16OVA Murine Melanoma

Anti-CTLA-4 Antibodies

OVA Rechallenge to Animals Surviving 40 Days

Used as Control with Sham IgG Antibodies

Significant Increase in Percentage Survival Versus Control

(p < 0.05)

OVA kb Tetramer Positive CD8b + T Cells After 10 Days

0.1% of CD8b + T Cells

4.2% of CD8b + T Cells

Anti-CD25 Antibodies

OVA Rechallenge to Animals Surviving 40 Days

Used as Control with Sham IgG Antibodies

Significant Increase in Percentage Survival Versus Control

(p < 0.05)

OVA kb Tetramer Positive CD8b + T Cells After 10 Days

0.1% of CD8b + T Cells

2.8% of CD8b + T Cells

Dromi, S.A., et al. [36]

MB49 Murine Urothethial Carcinoma

Intratumoral Injection of Immature Ex-Vivo Dendritic Cells

Median Tumor Volume Change

Significant Volume Loss Versus Control

(p < 0.05 versus Control)

No Significance Established Versus Control or Monotherapy

(p = 0.07)

Nakagawa, H., et al. [38]

MC38 Murine Colon Cancer

Local Injection of OK-432 Stimulated Dendritic Cells

Mean Tumor Volume 10 Days After Treatment

No Significant Established Versus Control

Significant Volume Loss Versus Monotherapy

(p < 0.001)

CD4+ T Cell Infiltration into Untreated Tumors 10 Days After Treatment

Significantly Increased

Versus Control

(p < 0.001)

Significantly Increased Versus Control & Monotherapy

(p < 0.001)

CD8+ T Cell Infiltration into Untreated Tumors

10 Days After Treatment

Significantly Increased

Versus Control

(p < 0.001)

Significantly Increased Versus Control & Monotherapy

(p < 0.001)

Liu, Q., et al. [39]

B16F10-luc Murine Melanoma

Heat-shocked Tumor Cell Lysate-pulsed Dendritic Cells

Percent Survival 100 Days After Treatment

No Data

Significantly Increased Versus Combination with Unheated Tumor Cell Lysate Pulsed DC’s (p < 0.01)

IFN-γ Produced by CD+ T Cells Isolated From Draining Lymph Nodes After 2 Weeks

No Data

Significantly Increased Versus Combination with Unheated Tumor Cell Lysate Pulsed DC’s

(p < 0.01)

Gameiro, S.R., et al. [40]

MC38 CEA+ Murine Colon Cancer

Poxviral Vaccine Expressing CEA and a TRIad of Costimulatory Molecules (CEA/TRICOM)

Primary & Distal Tumor Burden at Day 24

Combined Volume Significantly Reduced Versus Control

(p < 0.0001)

Combined Volume Significantly Reduced Versus Monotherapy

(p < 0.0054)

Relapse Free Survival

34.5% Animals Achieved Tumor Eradication

50% Subsequently Relapsed

52% Animals Achieved Tumor Eradication

30.8% Subsequently Relapsed

Iida, N., et al., [41]

BNL 1ME A.7R.1 Murine Hepatoma

Active Variant of CC Chemokine Ligand 3 (ECI301)

Tumor Volume After 14 Days

Significantly Reduced Compared to Control

(p < 0.01)

Significantly Reduced Versus Monotherapy

(p < 0.05)

CD4+ & CD8+ T Cell Infiltration After 3 Days

Significantly Increased Versus Control

(p < 0.01)

Significantly Increased Versus Monotherapy

(p < 0.01)

Shi, L., et al. [16]

CT26 Murine Colon Cancer

Anti-PD-1 Antibodies

Tumor Volume After 30 Days

No Significance Established Versus Control

Significantly Reduced Versus Monotherapy

(p < 0.001)

Total Survival After Inoculation

No Significance Established Versus Control

Significantly Prolonged Survival Versus Monotherapy

(p < 0.001)

  1. Cytolytic activity as measured by relative luminescence units (RLU) of adenylate kinase released by isolated peripheral blood T cells
  2. NS, not significant