Fig. 2: 90Y-NM600 + early/intermediate-timed ICI enhances therapeutic response in the immune sensitive MC38 colorectal carcinoma model. | Nature Communications

Fig. 2: 90Y-NM600 + early/intermediate-timed ICI enhances therapeutic response in the immune sensitive MC38 colorectal carcinoma model.

From: Priming versus propagating: distinct immune effects of alpha- versus beta-particle emitting radiopharmaceuticals when combined with immune checkpoint inhibition in mice

Fig. 2: 90Y-NM600 + early/intermediate-timed ICI enhances therapeutic response in the immune sensitive MC38 colorectal carcinoma model.The alternative text for this image may have been generated using AI.

A Treatment regimen options for in vivo therapy studies. Mice either received early (days −3/0/3), intermediate (days 4/7/10), or delayed (days 11/14/17) dual anti-CTLA4 and anti-PD-L1 relative to RPT on day 1. B–I MC38 tumor-bearing mice were randomized to one of 16 treatment groups: IgG2b control on days −5/0/5 (IgG2b), dual anti-CTLA4 and anti-PD-L1 (ICI) on days −3/0/3, days 4/7/10, or days 11/14/17, 2 Gy 90Y-NM600 (0.925 MBq), 177Lu-NM600 (1.85 MBq), or 225Ac-NM600 (4.625 kBq) on day 1, or combination 2 Gy 90Y-, 177Lu-, 225Ac-NM600 on day 1 with dual ICI on days −3/0/3, days 4/7/10, or days 11/14/17. B–D Individual MC38 tumor growth curves corresponding to (F, G). F, H Effects of varied ICI timing for each radionuclide on tumor growth and overall survival. G, I Effects of varied radionuclide for each ICI timing of combination therapy on tumor growth and overall survival. 90Y-, 177Lu-, 225Ac-NM600, and no RPT + early ICI extended overall survival compared to IgG2b. B–G Results of one experiment. H, I Results of two independent experiments. B–G N = 7: 90Y-, 177Lu-, 225Ac-NM600 ± ICI −3/0/3, ICI −3/0/3, IgG2b; n = 5: 90Y-, 177Lu-, 225Ac-NM600 + ICI 4/7/10 or + ICI 11/14/17, ICI 4/7/10, ICI 11/14/17. H, I N = 24: ICI −3/0/3, IgG2b; n = 17: 90Y-, 177Lu-, 225Ac-NM600 ICI −3/0/3; n = 10: ICI 4/7/10, ICI 11/14/17; n = 5: 90Y-, 177Lu-, 225Ac-NM600 + ICI 4/7/10 or + ICI 11/14/17. Linear mixed models were used to compare tumor volumes over time between various treatment groups. Statistical testing of the pairwise contrasts was adjusted for multiple comparisons using Tukey’s method. Log-rank test was used to compare survival. Error bars are SEM.

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