Cellular immune responses to recipient-derived leukemic blasts before and after immunizations (ELISPOT)
. | GrB spots/106 PBMCs . | . | . | IFN-γ spots/106 PBMCs . | . | . | IL-5 spots/106 PBMCs . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pt/dosage and preincubation* . | Before study . | After 3 injections† . | After 6 injections . | Before study . | After 3 injections . | After 6 injections‡ . | Before study . | After 3 injections . | After 6 injections§ . | ||||||
| 2/1 | |||||||||||||||
| None | 0 | 265 | 85 | 0 | 0 | 39 | 0 | 31 | 891 | ||||||
| Anti-CD4 | 0 | 0 | 18 | 0 | 0 | 0 | 0 | 7 | 102 | ||||||
| Anti-CD8 | 0 | 173 | 75 | 0 | 0 | 0 | 0 | 48 | 872 | ||||||
| 3/1 | |||||||||||||||
| None | 0 | 33 | 258 | 3 | 0 | 0 | 0 | 2 | 2 | ||||||
| Anti-CD4 | 0 | 20 | 0 | 0 | NE | NE | NE | NE | NE | ||||||
| Anti-CD8 | 0 | 0 | 0 | 0 | NE | NE | NE | NE | NE | ||||||
| 4/1 | |||||||||||||||
| None | 3 | 73 | 123 | 0 | 23 | 17 | 0 | 52 | 174 | ||||||
| Anti-CD4 | 0 | 8 | 33 | 0 | 3 | 4 | 0 | 3 | 2 | ||||||
| Anti-CD8 | 0 | 0 | 8 | 0 | 0 | 11 | 0 | 35 | 354 | ||||||
| 7/2 | |||||||||||||||
| None | 10 | 0 | 0 | 0 | 108 | 235 | 0 | 3 | 15 | ||||||
| Anti-CD4 | 0 | 5 | 3 | 0 | 5 | 30 | 0 | 5 | 0 | ||||||
| Anti-CD8 | 0 | 3 | 0 | 0 | 60 | 100 | 0 | 0 | 0 | ||||||
| 9/3 | |||||||||||||||
| None | 0 | 23 | 33 | 0 | 74 | 60 | 0 | 0 | 10 | ||||||
| Anti-CD4 | 0 | 0 | 10 | 0 | NE | 3 | 0 | NE | 0 | ||||||
| Anti-CD8 | 0 | 0 | 0 | 0 | NE | 99 | 0 | NE | 7 | ||||||
| 10/3 | |||||||||||||||
| None | 23 | 230 | 30 | 0 | 5 | 7 | 0 | 0 | 0 | ||||||
| Anti-CD4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||
| Anti-CD8 | 0 | 0 | 0 | 0 | 5 | 2 | 0 | 0 | 0 | ||||||
. | GrB spots/106 PBMCs . | . | . | IFN-γ spots/106 PBMCs . | . | . | IL-5 spots/106 PBMCs . | . | . | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pt/dosage and preincubation* . | Before study . | After 3 injections† . | After 6 injections . | Before study . | After 3 injections . | After 6 injections‡ . | Before study . | After 3 injections . | After 6 injections§ . | ||||||
| 2/1 | |||||||||||||||
| None | 0 | 265 | 85 | 0 | 0 | 39 | 0 | 31 | 891 | ||||||
| Anti-CD4 | 0 | 0 | 18 | 0 | 0 | 0 | 0 | 7 | 102 | ||||||
| Anti-CD8 | 0 | 173 | 75 | 0 | 0 | 0 | 0 | 48 | 872 | ||||||
| 3/1 | |||||||||||||||
| None | 0 | 33 | 258 | 3 | 0 | 0 | 0 | 2 | 2 | ||||||
| Anti-CD4 | 0 | 20 | 0 | 0 | NE | NE | NE | NE | NE | ||||||
| Anti-CD8 | 0 | 0 | 0 | 0 | NE | NE | NE | NE | NE | ||||||
| 4/1 | |||||||||||||||
| None | 3 | 73 | 123 | 0 | 23 | 17 | 0 | 52 | 174 | ||||||
| Anti-CD4 | 0 | 8 | 33 | 0 | 3 | 4 | 0 | 3 | 2 | ||||||
| Anti-CD8 | 0 | 0 | 8 | 0 | 0 | 11 | 0 | 35 | 354 | ||||||
| 7/2 | |||||||||||||||
| None | 10 | 0 | 0 | 0 | 108 | 235 | 0 | 3 | 15 | ||||||
| Anti-CD4 | 0 | 5 | 3 | 0 | 5 | 30 | 0 | 5 | 0 | ||||||
| Anti-CD8 | 0 | 3 | 0 | 0 | 60 | 100 | 0 | 0 | 0 | ||||||
| 9/3 | |||||||||||||||
| None | 0 | 23 | 33 | 0 | 74 | 60 | 0 | 0 | 10 | ||||||
| Anti-CD4 | 0 | 0 | 10 | 0 | NE | 3 | 0 | NE | 0 | ||||||
| Anti-CD8 | 0 | 0 | 0 | 0 | NE | 99 | 0 | NE | 7 | ||||||
| 10/3 | |||||||||||||||
| None | 23 | 230 | 30 | 0 | 5 | 7 | 0 | 0 | 0 | ||||||
| Anti-CD4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||
| Anti-CD8 | 0 | 0 | 0 | 0 | 5 | 2 | 0 | 0 | 0 | ||||||
Patient 1 (dose level 1) experienced early disease progression. Patient 5 (dose level 2) did not have enough blasts for immunologic studies. Patients 6 (dose level 2) and 8 (dose level 3) had 0 GrB, IFN-γ, and IL-5 spots per 106 PBMCs.
Pt indicates patient; PBMCs, peripheral blood mononuclear cells; and NE, not enough blasts for immunologic studies.
The dose-escalation schedule began at 2 × 105 CD40L-secreting skin fibroblasts per injection (dose level 1), increasing in log increments to 2 × 107 (dose level 3). IL-2-secreting skin fibroblasts and recipient-derived blasts were administered at a fixed dosage throughout the study (2 × 107 per injection)
Increase in GrB secretion was statistically significant after 3 immunizations compared with prevaccination values (P = .046)
Increase in IFN-γ secretion was statistically significant after 6 immunizations compared with prevaccination values (P = .046)
Increase in IL-5 secretion was statistically significant after 6 immunizations compared with prevaccination values (P = .043)