Immunotherapy for Medullary Thyroid Carcinoma by Dendritic Cell Vaccination

Clinical response to DC vaccination

Clinical response to DC vaccination

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Summary

The goal of this study was to develop a DC vaccination therapy in patients with metastasized medullary thyroid carcinoma (MTC). The data indicates that vaccination with calcitonin and/or CEA peptide-pulsed DC results in the induction of a cellular, antigen-specific immune response in patients with MTC, leading to clinical response in some patients.

Patients characteristics

7 patients ages 31-62 years old with histologically proven medullary thyroid carcinoma (MTC) with radiologically established disease or with postoperative elevated plasma calcitonin.

Methodology

Vaccine preparation
PBMCs were allowed to adhere to plastic dishes, and adherent cells were cultured for 6 days with granulocyte macrophage colony-stimulating factor (800 U/ml) and IL-4 (500 U/ml). On day 6, DCs were washed and cultured with granulocyte macrophage colony-stimulating factor (800 U/ml), TNFa (1000 U/ml), and antigen. DCs (5 x 106) were pulsed with CEA and calcitonin (10 μg and 100 μg/ml per 1 x 106 DCs).

Treatment

Antigen-pulsed DCs (1–5 x 106 cells in 100 μl 0.9% NaCl) were administered by intracutaneous injections in the upper arm. The first four treatments were administered weekly, whereas the following vaccinations were given at intervals of 4–8 weeks.

Results

DC vaccination was well tolerated by all patients. There were no serious adverse effects or any clinical signs of autoimmune reaction.During follow-up (mean, 13.1 months) three of seven patients (43%) developed a clinically measurable response after DC vaccination, of whom one (patient 3, 37 years old with liver, lung, skin metastasis) had a partial response (PR) and two other patients (1 and 7 both have liver metastasis) developed a mixed response. Patient 3 developed complete regression of all detectable liver metastases and a significant regression of pulmonary metastases.Patient (no.1) developed a mixed response with a steady decrease of serum calcitonin by 30% during the first 5 months of DC immunotherapy.Four of seven patients (patients 2, 4, 5, and 6) had a stable disease without biochemical or morphological (CT scan, ultrasound) signs of growing tumour masses.

Conclusion

In conclusion, this is the first trial on a DC vaccination in patients with MTC demonstrating a beneficial effect in some patients. The observations strongly suggest that DC immunotherapy using CEA and/or calcitonin represents a promising therapeutic approach in yet untreatable forms of MTC.

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Scientific article publishing date: 10/1/2001

Immucura identifier BSC21_335EN

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