Table 3.
Previous MPE immunotherapy clinical trials.
| Treatment | Design | Patients | Response # (%) | Adverse Events | Ref |
|---|---|---|---|---|---|
| IL-2 | Phase 1 trial of continuous intrapleural rIL-2 infusion | n = 22 adeno-6, meso-15, squam-1 |
CR 1 (5) PR 9 (41) |
Accepted tolerance with some side effects: fever/chills, 2 meso died | 168 |
| IL-2 and LAK | Lymphokine activated killer cells used with IL-2 to treat effusions from lung cancer | n = 33 | CR 18 (55) PR 12 (36) NR 3 (9) |
No serious side effects | 169 |
| IL-2 | Intrapleural and follow up subcutaneous administration of IL-2 providing palliation of pleural effusion and on primary tumor | n = 31 | ORR 7 (22) SD 10 (32) PD 14 (24) |
Manageable toxicity | 173 |
| IL-2 | IL-2 therapy reverses the exhaustion phenotype of MPE CD8 + T cells. Initially low Granzyme B, IFN- γ, and proliferation with high PD-1 expression is reversed to reduce IL-2 expression and increase the others in MPE. Carcino-embryonic antigen reduced by IL-2 | n = 35 (lung cancer) and 12 non-MPE |
IL‐2 treatment reduced the expression of PD‐1, increased the expression of Granzyme B and IFN-γ and enhanced the proliferation of CD8+ T cells in MPE | Dose-dependent severity ranging from fever to abnormal renal function | 170 |
| OK432 | Pilot study using autologous lymphocytes activated ex vivo and monocyte-derived dendritic cells in combination with low-dose OK432 | n = 5 | Decreased effusion production in all pts. | No severe AEs | 174 |
| IFN-α2b | Comparing bleomycin (chemotherapy) to IFN-α2b (immunotherapy). Effusion drained and then given either treatment. Second dose of bleomycin administered for nonresponsive patients. Treatment groups were randomly assigned | n = 160 (83 bleomycin, 77 IFN-α2b) |
30 Day Response Bleomycin: 70 (84.3) IFN-α2b: 48 (62.3) |
None listed | 175 |
| IFN-β | Phase 1 ranging single-dose intrapleural IFN-beta gene transfer by adenoviral vector through indwelling pleural catheter. Evaluates toxicity, gene transfer, and immune, and tumor responses. | n = 10, 7 MPM, 3 MPE |
Gene transfer 7 (70) Antitumor immune response 7 (70) SD 4 (40) PR 4 (40) |
Well tolerated, transient lymphopenia most common. Max tolerated 9E11 viral particles |
176 |
| DCs | Open label pilot study treating MPE patients with DCs derived from autologous CD34+ stem cells stimulated with IL-4, GM-CSF, TNF-α, | n = 26 | CR 1 (3.8) PR 13 (50) SD 10 (38.5) PD 5 (19.2) |
No severe AEs | 119 |
| DCs and cyclophosphamide | Pilot studying using cyclophosphamide and autologous DCs pulsed with MM tumor lysate prior to chemotherapy and P/D. | n = 10 | CR 1 (10) SD 4 (40) PD 2 (20) N/A 3 (30) 8/10 Radiographic improvement Median OS 26 Months |
Well tolerated without systemic toxicity, except for transient fatigue and low-grade fever on the day of the DC injection. No grade 3 or higher AEs. |
120,121 |
| αCD25 +IL-2 +OK432 |
Low-dose anti-CD25 antibody to target T-reg cells. Low concentration of basiliximab augments) production in combination with IL-2. Can also be followed by administration of OK432. Foxp3 expression of ELs (effusion lymphocytes) not definitively changed. Aims to evaluate efficacy of basiliximab followed by OK432 administration (day 0 or 1) | n = 12 | CR 2 (16.7) PR 5 (41.7) |
Safe and well tolerated | 177 |
| CIK Cell Therapy | DC and CIK (cytokine-induced killer) cells treat MPE | n = 16 and 15 control |
CR 8 (50) PR 5 (31.3) NR 3 (18.8) |
Grade III or below, most commonly fever in both groups | 178 |
| Viral Therapy | Phase 1 dose escalation of GMCI strategy with vector for thymidine-kinase gene followed by valacyclovir with chemotherapy, celecoxib added to reduce CRS. | n = 19, 17 evaluable | PR 4 (23.5) SD 9 (52.9) PD 4 (23.5) |
Well tolerated without DLTs | 179 |
Key: Interleukin-2 (IL-2), Recombinant IL-2 (rIL-2), Lymphocyte Activated Killer Cell (LAK), Complete Response (CR), Partial Response (PR), No Response (NR), Progressive Disease (PD), Adverse Events (AEs), Pleurectomy with Decortication(P/D) Interferon Gamma (IFN- γ), Programmed Death Receptor 1 (PD-1), Dendritic Cells (DCs), Els, CIK, GMCI (gene-mediated cytotoxic immune), Cytokine Release Syndrome (CRS), DLTs (Disease Limiting Toxicities).