The current strategy in the field of cancer treatment employs tandem lines of therapies directed either to kill tumour cells directly or to encourage the body’s immune response to kill them. Animesh Kar, Dolly Jain, Avinash Bajaj, and Ujjaini Dasgupta, working on the hydrogel-mediated delivery of anticancer drugs, have achieved both goals with their latest innovation.
The novelty of this drug is the claim of a reduction in the widespread toxicity observed with most chemotherapies. The authors propose that DTX-CPT-Gel be administered close to the tumour. In contrast, the usual delivery of chemotherapeutic drugs involves injection into the veins (intravenous), circulating them through the body. An injection site closer to the tumour will avoid unintended effects on faraway tissues. The authors claim that the process of this drug will be no more invasive than intravenous injections. Dolly Jain says,
The hydrogel can be administered directly near the tumour site through direct injection or localised application, making it minimally invasive.
The authors found the drug release from the hydrogel to be continuous and sustained. This controlled release is necessary as per Dasgupta, “DTX-CPT-Gel may be beneficial for cancers that are less responsive to immunotherapy or when a combination therapy approach is needed.” The two drugs, DTX and CPT, are known to be deadly to cells (cytotoxic), and a ratio of 2:1 of DTX: CPT packaged in hydrogels exhibited the most potent cytotoxic capability.
The uniqueness of these dying cells is the release of certain biomolecules known as damage-associated molecular patterns (DAMPs). The release of DAMPs by dying tumour cells activates dendritic cells, which usually patrol most tissues. Dendritic cells usually cannot recognise cancer cells as foreign, and do not attack them. However, the DAMP molecules are identified by dendritic cells, which readies them for an attack on cancer cells.
Activated dendritic cells also feed into the memory arm of the immune response. These DAMP-activated dendritic cells help specific immune cells (T cells) to further attack cancer cells and retain memory of their structure for surveillance. The authors thus present a reinforcing loop of these two kinds of cell death, where the antitumour drug-mediated cell death leads to the secretion of unique “eat-me” molecules (DAMPs) that instigate immune T cells to identify the same signals in nearby tumour cells and kill them.
The drug primes CD8+ T cells efficiently, as they also help eliminate tumours arising in distant organs. The authors ensured that this T cell-mediated elimination of distant tumours is specific to the tumour type. The memory of these T cells provides systemic protection to the mice, as the same tumour cells arising in distant organs are effectively destroyed. This T cell-mediated surveillance is precise since the authors found that T cells do not attack cancer cells of any other type.
The elicited immune response is thus highly discrete — not only does it distinguish cancer cells from normal, but it also identifies the type of cancer cells. This identification is due to specific proteins, along with the generic DAMPs secreted by the dying primary tumour cells. These tumour-specific antigens (neoantigens) are not yet discovered by the team. Bajaj says, “We have not pinpointed the precise neoantigens. We intend to elucidate this aspect in our forthcoming research endeavours.”