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Table 3 Clinical studies of cell therapies for RCC treatment

From: Evolution of cell therapy for renal cell carcinoma

Phase

Clinical design

Clinical response

Author

I

Treatment: CD70-targeting allogeneic CAR-T cell therapy (CTX-130™).

Protocol: Standard lymphodepleting chemotherapy with fludarabine 30 mg/m² and cyclophosphamide 500 mg/m² for 3 days, followed by CTX-130™ infusion at dose levels ranging from 3 × 107 to 9 × 108.

7.7% durable CR (18 + months) and 69.2% SD (4 months).

Pal et al. 2022 [40]

I

Treatment: Autologous T cells genetically retargeted against CAIX CD4 gamma-based CAR-T cells.

Protocol: T cells expressing scFvG250-CD4 gamma receptor.

Cohort 1: Inpatient up titration; max 8 IV infusions with 2 × 107 a 2 × 109 T cells each in two cycles, combined with 5 × 105 IU/m2 human rIL-2 SC, twice a day at days 1–10 and 17–26.

Cohort 2: 3 × 3 Phase I approach, start dose: 1 × 108 T cells/ infusion at a maximum of 10 infusions in two cycles; combined with 5 × 105 IU/m2 human rIL-2 SC, twice a day at days 1–10 and 29–38.

Cohort 3: same as cohort 2 plus pre-treatment with 5 mg anti-CAIX mAb G250 IV infusion 3 days before start each series of T cell infusions.

12 patients with no clinical responses recorded.

Lamers et al. 2006, 2013 [41, 42]

I/II

Treatment: DC vaccination.

Protocol: Antigen-pulsed autologous dendritic cells. Intranodal or intradermal vaccinations at a 1 × 107 dose (at least 6 vaccinations): 4 vaccinations: 1/27; 6 vaccinations: 14/27; 7–27 vaccinations: 12/27. Second vaccination was combined with 2 × 106 IU IL-2 SC (days 2–6) and 18/27 patients received 5% imiquimod topical (2–6 hs before vaccination).

Response after 8 weeks:

13/27 SD and 14/27 PD.

Median overall survival: 16.6 months.

Berntsen et al. 2008 [43]

I

Treatment: LANAK cells associated with IL-2 infusions.

Protocol: IL-2 Cycles at 1-week intervals (at a daily dose of 16-20 × 106 IU/m2 infused alone for 48 h), apheresis 2 days after the end of each course, followed by reinfusion of LANAK cells (prepared in vitro) 2 weeks after apheresis + a 3-day cycle of 16-20 × 106 IU/m2IL-2 daily.

3/10 PR, 4/10 CR and 1/10 SD with immunotherapy alone, and 2/10 CR after immunotherapy plus surgery.

Escudier et al. 1994 [44]

I

Treatment: Autologous cell-therapy product based on γ9δ2 T cells (Innacell γδ™).

Protocol: 3 cycles of 1-h intravenous infusion of γ9δ2 T cells with 3-week intervals (doses from 1 up to 8 × 109 cells), combined with IL-2 SC (2 × 106 IU/m2 from DAY 1 to 7) in the second and third cycles.

6/10 SD, 4/10 PD and 25.7 weeks median time to progression.

Bennouna et al. 2008 [45]

II

Treatment: LAK cells with human rIL-2.

Protocol: 48/94 continuous infusion arm group: rIL-2 1 mg/m²/d IV infusion. LAK cells administered IV on days 11,12 and 14. 46/94 bolus injection group: rIL-2 33 µg/kg IV bolus infusion. LAK cells administered IV on days 11, 12 and 14. Both groups: one course of treatment every 3 months (3 courses total).

Bolus injection: 3/46 CR and 6/46 PR.

Continuous infusion: 2/48 CR and 5/48 PR.

Weiss et al. 1992 [46]

I

Treatment: Autologous CIK cells in combination with DCs and tyrosine kinase TKIs

Protocol: Group 1: sunitinib/sorafenib monotherapy; Group 2: DCs + auto-CIKs + sunitinib/sorafenib

Significantly higher median PFS (28.0 vs. 11.0 months); 3-year OS rate (57.1% vs. 28.6%); more SD (11/15 vs. 6/19); less PD (8/15 vs. 9/19), and death (3 vs. 5) in group 2 compared to group 1.

Mai et al. 2018 [47]

I

Treatment: Autologous CIK cells in combination with DCs and pembrolizumab (anti PD-1)

Protocol: 31 patients assessed for response to treatment with DCs + auto-CIKs + pembrolizumab. All patients enrolled in trial were given the therapeutic.

2/31 CR, 5/31 PR, 13/31 SD and 11/31 PD (1/8 CR, 1/8 PR, 4/8 SD, 2/8 PD in RCC); Overall disease control rate is 64.5%

Chen et al. 2018 [48]

  1. RCC Renal cell carcinoma, PD Progressive disease, SD Stable disease, PR Partial response, CR Complete response, GvHD Graft-versus-host disease, CRS Cytokine release syndrome, GR Grade, CAIX Carbonic anhydrase IX, scFv Single-chain variable fragment, IV Intravenous, SC Subcutaneous, mAb Monoclonal antibody, rIL-2 Recombinant interleukin-2, LANAK Lymphokine-activated natural killer, CIK Cytokine-induced killer cells, TKI Tyrosine kinase inhibitors, LAK Lymphokine-activated killer cells, DC Dendritic cells