Table 1.
Advancements of NK cell transfer, NK cell engagers and Cytokine-based NK cell activation for hematologic and solid tumors
| Type of therapy | Adoptive NK cell transfer | NK cell engagers | Cytokine-based NK cell activation | ||
|---|---|---|---|---|---|
| Authors (reference) | Ranalli [2] | Kim [3] | Le [4] | Lee [5] | Gong [6] |
| Trial identifier (Phase) | NCT04211675 (II) | NCT05109442 (I/II) | NCT05727839 (I) | NCT05824975 (I/II) | NCT05666635 (I) |
| Agents | UD-TGFβi NK cells + irinotecan + temozolomide + dinutuximab | AFM24 (a bispecific, tetravalent innate cell engager) + atezolizumab | JCXH-211, a self-replicating mRNA encoding IL-12 | GI-102 (CD80-IL2v3) | LTC004, a novel IL-2Rβ/γ cytokine agonist |
| Malignancy | R/R Neuroblastoma | EGFR -WT non-small cell lung cancer | Malignant solid tumors | Advanced or metastatic solid tumors | Advanced solid tumors |
| Patient number | 4 | 17 | 10 | 32 | 17 |
| Male | N/A | 82.4% | N/A | N/A | N/A |
| Median Age and (or) range (years) | 7–11 | 66(45–75) | N/A | N/A | N/A |
| Clinical trial design | 21-day cycles of CIT as per COG protocol ANBL1221 with UD-TGFbi NK cells (1 × 108 cells/kg) infused on day 8 | Phase 2 dose of 480 mg AFM24 was given IV weekly in combination with 840 mg atezolizumab IV fortnightly | JCXH-211 at 5, 25, 50, and 100 mg were given Q4W. Dose Limiting Toxicities were monitored for 28 days after first dose | GI-102 was administered IV Q3W until disease progression or unacceptable toxicities | Dose escalation part assessed safety and tolerability of LTC004 with doses ranging from 3.0 to 360 µg/kg IV Q3W |
| Median Follow-up (months) | N/A | 5.5 | N/A | N/A | N/A |
| Response rate | PR 75% | ORR 26.7% | NA | ORR 17.4% | ORR 5.9%, DCR 58.5% |
| Survival | N/A | N/A | N/A | N/A | N/A |
| Summary | It could be safely and feasibly administered to children with R/R NBL after treatment with CIT | It shows remarkable signs of clinical efficacy, even in patients with resistance to prior CPI, and a well-tolerated and manageable safety profile | It demonstrates good safety profile. Antitumor activities were observed in the heavily pretreated late-stage patients | GI-102 is well tolerated up to dose of 0.45 mg/kg Q3W, in patients who failed on standard of care | It shows encouraging anti-tumor efficacy, and well tolerated in patients with advanced or metastatic solid tumors |
CIT chemoimmunotherapy, CPI checkpoint inhibitor, DCR, disease control rate, EGFR epidermal growth factor receptor, IV intravenously, LAG-3 lymphocyte-activation gene 3, N/A not available, NBL Neuroblastoma, NHL non-Hodgkin lymphoma, NK Natural killer, NKG2A NK cell lectin-like receptor subfamily C member 1, ORR objective response rate, PR partial response, Q3W, once every 3 weeks, R/R relapsed or refractory, TGFβi TGFβ-induced suppression, UD universal donor, WT wide type