Tucotuzumab celmoleukin

BALB/c (6- to 8-wk-old female; injected s.c. with 5×10⁵ CT26-KS colon adenocarcinoma cells in the abdomen)^[1]

15 μg (subtherapeutic single agent; combination therapy); 37.5 μg (combination therapy)

i.t.; daily for 5 days (15 μg); 2 doses (37.5 μg)

Resulted in moderate tumor growth suppression compared with no treatment (P = 0.002), but no complete tumor resolution when used alone with subtherapeutic dosing (15 μg i.t.
days 11-15).
Achieved synergistic tumor growth suppression (P < 0.001 on day 16 and P < 0.002 on day 19 versus all other groups), complete tumor resolution in 8 of 16 mice, and significantly enhanced survival compared with untreated mice (P < 0.001), RFA alone (P < 0.001), or Tucotuzumab celmoleukin alone (P = 0.002) when combined with partial RFA.
Across all experiments, combination therapy resulted in complete tumor resolution in 14 of 28 mice (P < 0.001 versus no treatment, P = 0.024 versus RFA alone, P = 0.003 versus Tucotuzumab celmoleukin alone).
Showed tumor growth suppression not significantly different from the 5-day 15 μg dose regimen, and both were superior to RFA alone (P < 0.005 on day 25) when given as two 37.5 μg i.t.
doses (days 10 and 14) in combination with RFA.
Resulted in complete resolution of the treated abdominal tumor in 7 of 15 mice and complete resolution of the untreated distant flank tumor in 8 of 15 mice as a single agent (15 μg i.t.
days 10-14).
Enabled tumor-free mice treated alone or in combination with RFA to reject rechallenges with CT26-KS tumor cells, and 3 of 3 mice treated alone to reject parental CT26 tumor rechallenges.
Induced 3% of CD4⁺ T cells and 5-6% of CD8⁺ T cells expressing IFN-γ after in vitro stimulation with CT26-KS cells in splenocytes from mice treated alone, with similar low proportions expressing GM-CSF.