Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial

SLN cumulative response

SLN cumulative response

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Summary

This trial confirms the safety of neoadjuvant DC1 vaccination for patients with early invasive breast cancer (IBC). The immune response in the sentinel lymph nodes, may serve as an endpoint more reflective of antitumor activity.

Patients characteristics

54 Female patients ages 35-83 years old with the median age of 55 years with biopsy-proven
HER2pos DCIS, DCIS with microinvasion, DCIS with invasive disease less than 5 mm, or Paget disease of the nipple who had not yet received definitive treatment. The majority of patients were postmenopausal (84.0%) and white (80.2%). Most tumors were high grade (71.7%) with 3+ HER2 expression (64.8%).

Methodology

Patients underwent tandem apheresis/ countercurrent centrifugal elutriation to isolate monocytic DC precursors. Cells were pulsed with six HER2 MHC class II binding peptides: three extracellular domain peptides and three intracellular domain peptides, and rapidly matured to a DC1 phenotype by adding IFNg and LPS. The monocytes of HLA-A2POS and HLA-A3POS patients were also pulsed with two HER2 MHC class I binding peptides.

Treatment

Six weekly injections of 1–2×107 HER2 peptide-pulsed DC1s were administered into the breast (IL; n=19), into the groin lymph nodes (IN; n= 19), or half of the dose into the breast and half of the dose into the groin lymph nodes (ILN; n=16).
Following each weekly vaccination, patients were monitored for adverse effects for a minimum of 1 to 2 hours. Each patient underwent cardiac evaluation including multi-gated acquisition (MUGA) scan or echocardiogram prior to vaccination and within 2 weeks of the final vaccination.
Randomized treatment allocation was as follows: 19 patients (35.2%) received intralesional (IL) injections, 19 patients (35.2%) received intranodal (IN) injections, and 16 patients (29.6%) received intralesional and intranodal (ILN) injections.

Results

Adverse events
Overall, the vaccine was well tolerated with only grade 1 (n=37, 68.5%) and grade 2 (n=15, 27.8%) adverse events reported. The most commonly reported adverse events associated with the vaccine were fatigue (n=22, 40.7%), injection site reaction (n=22, 40.7%), and chills/rigors (n=14,25.9%). All of the patients received all six vaccine injections, and none of the patients withdrew from the trial due to the experienced side effects. The route of injection did not affect the risk of adverse events with grade 1–2 vaccine- related adverse events reported in 73.7% of patients who received IL injections, 68.4% of patients who received IN injections, and 75.0% of patients who received ILN injections. Only 2 patients exhibited asymptomatic declines in left ventricular ejection fraction (EF); one patient who received IL injection exhibited a decrease in EF to 55% (an 18% decrease), which subsequently returned to baseline within 30 days, and one patient who received ILN injection exhibited a decrease in EF to 49% on MUGA (a 28% decrease), which was attributed to PVCs and was not evident when immediately reevaluated by echocardiogram (EF, 60%–65%).
Immune response
On the basis of 53 vaccinated patients evaluable for immune responses, 43 (81.1%) had new or increased immune responses detected in the peripheral blood following vaccination. The immune response rates (exact 95% CI) by route of vaccination were as follows: IL 84.2 (60.4%– 96.6%), IN 89.5% (66.9%–98.7%), and ILN 66.7% (38.4%–88.2%).
Clinical Response
Clinically, 13 patients had no disease in the surgical specimen at the time of surgical resection, achieving a pathological complete response (pCR). Patients with DCIS achieved a higher rate of pCR (12/42, 28.6%) compared with patients with invasive disease (1/12, 8.3%).In DCIS patients, the rate of pCR was similar by route of injection (IL, 23.1%; IN, 31.3%; ILN, 30.8%).

Conclusion

This showed that DC1 vaccination remained safe and well tolerated independent of the route of vaccination. DC1 vaccination was also equally effective in inducing immune and clinical responses independent of the route of vaccination.

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Scientific article publishing date : 13/12/2016

Immucura identifier : BSC21_020EN

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